Trends in the Epidemiology of Pneumocystis Pneumonia in Immunocompromised Patients without HIV Infection

Abstract

The increasing morbidity and mortality of life-threatening Pneumocystis pneumonia (PCP) in immunocompromised people poses a global concern, prompting the World Health Organization to list it as one of the 19 priority invasive fungal diseases, calling for increased research and public health action. In response to this initiative, we provide this review on the epidemiology of PCP in non-HIV patients with various immunodeficient conditions, including the use of immunosuppressive agents, cancer therapies, solid organ and stem cell transplantation, autoimmune and inflammatory diseases, inherited or primary immunodeficiencies, and COVID-19. Special attention is given to the molecular epidemiology of PCP outbreaks in solid organ transplant recipients; the risk of PCP associated with the increasing use of immunodepleting monoclonal antibodies and a wide range of genetic defects causing primary immunodeficiency; the trend of concurrent infection of PCP in COVID-19; the prevalence of colonization; and the rising evidence supporting de novo infection rather than reactivation of latent infection in the pathogenesis of PCP. Additionally, we provide a concise discussion of the varying effects of different immunodeficient conditions on distinct components of the immune system. The objective of this review is to increase awareness and knowledge of PCP in non-HIV patients, thereby improving the early identification and treatment of patients susceptible to PCP.

Keywords: Pneumocystis; epidemiology; immunocompromised; immunodepleting monoclonal antibodies; non-HIV/AIDS; organ transplantation; primary immunodeficiency.

Figure 1

Pneumocystis infection chain. The infectious agent is exemplified by the cyst (also known as ascus) of P. murina in infected mouse lungs revealed by transmission electron microscopy at a magnification of 5000×. The cyst is characterized by a thick wall with double electron-dense layers enclosing eight intracystic bodies or spores. For the primary immunodeficiencies (under the Susceptible Host), only a limited number of conditions are listed as examples to enhance visual clarity, with more details described in Section 4.5.

Figure 2

The number of reports on PCP in transplant recipients from 1964 to 2022 based on search of PubMed using keywords “Pneumocystis AND Transplant” or “Pneumocystis AND Transplantation” in “Title/Abstract”.

Figure 3

Heatmaps depicting the incidences of co-infection with P. jirovecii and SARS-CoV-2. (A) The total incidences of co-infection with P. jirovecii and SARS-CoV-2 in patients regardless of HIV/AIDS. (B) The incidences of co-infection with P. jirovecii and SARS-CoV-2 in patients without HIV/AIDS. The number on the map represents the reported number of cases. Details on statistics and related references for all cases are provided in Supplemental Table S3.

Figure 4

Heatmap depicting the incidences of PCP outbreaks in transplant patients. The number on the map represents the reported number of cases regardless of whether genotyping analysis was conducted. Details on statistics and related references for all cases are provided in Supplemental Table S4.