Rising incidence of Pneumocystis pneumonia: a population-level descriptive ecological study in England

Publication summary

Risk for pneumonia caused by the fungus Pneumocystis jirovecii is associated with immunocompromising conditions such as uncontrolled HIV, transplant, lowered immunity caused by cancer or chemotherapy, and use of immunosuppressive and immunomodulatory therapies. Though Pneumocystis pneumonia was one of the early hallmarks of HIV infection, rates dropped dramatically in people living with HIV following the introduction of highly active antiretroviral therapy and targeted antimicrobial prophylaxis. In immunocompromised people who do not have HIV, however, the death rate associated with Pneumocystis pneumonia can surpass 50%, and no consensus-based guidelines exist for trimethoprim-sulfamethoxazole (co-trimoxazole) prophylaxis in populations other than people living with HIV and people with hematologic cancers. In addition to a lack of guidelines for many immunocompromised groups, very few studies in the past decade have assessed Pneumocystis jirovecii infections in people without HIV, though data from several European countries suggest that incidence is increasing. This study used an NHS dataset representing about 99% of all hospitals in England to evaluate trends in the incidence of Pneumocystis jirovecii pneumonia from Apr 1, 2012, to Mar 31, 2022, along with trends in the use of co-trimoxazole from Jan 1, 2019, to Apr 30, 2022.

Who this is for

• Clinicians working with immunocompromised people
• Developers of guidelines for fungal infection testing, prophylaxis, and treatment

Key findings

Pneumocystis pneumonia incidence in England: 2012–2022

• The incidence of Pneumocystis pneumonia episodes increased by 106% during the time period, with similar trends observed for Pneumocystis pneumonia as a primary or secondary diagnosis. During the same period, episodes associated with other invasive fungal infections (i.e., pulmonary or disseminated aspergillosis, cryptococcal disease, mucormycosis, and histoplasmosis) rose by 41%.
• Incidence increased from 2.2 episodes per 100,000 population at the beginning of the study period to 4.5 per 100,000 in 2019–2020. During the first year of the COVID-19 pandemic (2020–2021), incidence dropped to 2.7 per 100,000, then rose to 3.9 per 100,000 in 2021–2022.
• The proportion of Pneumocystis pneumonia admissions rose by 84% during the study period, from 6.5 per 100,000 all-cause hospital admissions to 11.3 per 100,000 admissions. As a proportion of all disseminated or respiratory fungal infections, the percentage of Pneumocystis pneumonia diagnoses rose from 67% to 74%.
• The rate of Pneumocystis pneumonia in patients 75 years of age and older increased from 14% to 26% during the time period. The median length of stay for patients with Pneumocystis pneumonia remained stable at 13.5 days.
• Use of intravenous co-trimoxazole, which is rarely used for infections other than those caused by Pneumocystis jirovecii in England, increased from January 2019 to April 2022, with a reduction in use observed during the first year of the COVID-19 pandemic (April 2020 to 2021).

Changes in risk for Pneumocystis pneumonia

The authors highlight the disparity between changing risk factors for Pneumocystis pneumonia—an aging population, a higher prevalence of immunomodulatory therapies, rising rates of autoimmune diseases and cancer—and the lack of consensus guidelines for prophylaxis in many of these populations, along with very few epidemiological studies to support evidence-informed guidelines.

Though the authors acknowledge that the results might be partly attributable to increases in use of polymerase chain reaction and biomarker tests, they also note that incidence of Pneumocystis pneumonia episodes was rising in English hospitals before the UK made these tests the standard for diagnosis. Another limitation includes the fact that the study could not distinguish patients living with HIV from those without HIV, though the low rate of undiagnosed and uncontrolled HIV infection in England makes it unlikely that people living with HIV would continue to be at high risk of Pneumocystis pneumonia.

In the company of a German study and a regional Norwegian analysis that both observed similar increases in incidence, this study represents one of the few efforts within the last decade to estimate population-level incidence of Pneumocystis pneumonia. Given the lack of up-to-date information on risk for Pneumocystis pneumonia and the lengthy and costly hospital stays required by those who are infected with Pneumocystis jirovecii, the researchers advocate for improved investments in research that better illuminates the populations who might benefit from antifungal prophylaxis.