Pneumocystis Pneumonia: Immunity, Vaccines, and Treatments

Abstract

For individuals who are immunocompromised, the opportunistic fungal pathogen Pneumocystis jirovecii is capable of causing life-threatening pneumonia as the causative agent of Pneumocystis pneumonia (PCP). PCP remains an acquired immunodeficiency disease (AIDS)-defining illness in the era of antiretroviral therapy. In addition, a rise in non-human immunodeficiency virus (HIV)-associated PCP has been observed due to increased usage of immunosuppressive and immunomodulating therapies. With the persistence of HIV-related PCP cases and associated morbidity and mortality, as well as difficult to diagnose non-HIV-related PCP cases, an improvement over current treatment and prevention standards is warranted. Current therapeutic strategies have primarily focused on the administration of trimethoprim-sulfamethoxazole, which is effective at disease prevention. However, current treatments are inadequate for treatment of PCP and prevention of PCP-related death, as evidenced by consistently high mortality rates for those hospitalized with PCP. There are no vaccines in clinical trials for the prevention of PCP, and significant obstacles exist that have slowed development, including host range specificity, and the inability to culture Pneumocystis spp. in vitro. In this review, we overview the immune response to Pneumocystis spp., and discuss current progress on novel vaccines and therapies currently in the preclinical and clinical pipeline.

No Statistically Apparent Difference in Antifungal Effectiveness Observed Among Trimethoprim/Sulfamethoxazole Plus Clindamycin or Caspofungin, and Trimethoprim/Sulfamethoxazole Monotherapy in HIV-Infected Patients with Moderate to Severe Pneumocystis Pneumonia: Results of an Observational Multicenter Cohort Study

“…The adverse events of TMP-SMX have been widely reported, and include rashes, fever, gastrointestinal complications, bone marrow suppression, hyperkalemia, hepatoxicity, and renal insufficiency [ 23 ]. The adverse effects of clindamycin and caspofungin are similar to those of TMP-SMX.…”

“…TMP-SMX exerts its effects on trophic forms of P. jirovecii , while caspofungin primarily acts on cystic forms of P. jirovecii [ 13 ], and the combination of caspofungin and TMP-SMX thus has the potential to inhibit the entire life cycle of the Pneumocystis organism [ 14 ]. Case reports have described the clinical success of caspofungin when used in combination with TMP-SMX in treating moderate to severe PCP in immunocompromised hosts [ 15 ]. A clinical trial involving caspofungin salvage treatment in HIV-infected patients with PCP has shown an appreciably high success rate (80%, 8/10 patients) [ 13 ].…”

A Negative (1,3)-β-D-Glucan Result Alone Is Not Sufficient to Rule Out a Diagnosis of Pneumocystis Pneumonia in Patients With Hematological Malignancies

“…Indeed, most of HM patients developing PCP have B-cell disorders, whereas SOT recipients as well as SAIID patients commonly receive chemical immunosuppressive drugs that mainly affect T-cells ( Kolls, 2017 ; Pallet et al, 2018 ). It is well-known that CD4+ T-cells play a key role in the clearance of P. jirovecii by promoting the recruitment of phagocytes to the infected lungs ( Gingerich et al, 2021 ). Thus, one may speculate that the high fungal loads and BG levels observed in SOT patients and SAIID patients are linked to an altered T-cell function.…”

Retinoids in Fungal Infections: From Bench to Bedside

“…Pneumocystis jiroveci is an unusual fungus of the genus Pneumocystis [44]. This fungus is the causative agent of Pneumocystis pneumonia (PcP), a common opportunistic disease in immunocompromised hosts, such as patients with AIDS [45] and those with other predisposing immune deficiencies [46]. Historically, PcP has been reported mainly in immunocompromised patients.…”