Pneumocystis jirovecii detection in asymptomatic patients: what does its natural history tell us?

Abstract

Pneumocystis jirovecii is an unusual ascomycetous fungus that can be detected in the lungs of healthy individuals. Transmission from human to human is one of its main characteristics in comparison with other fungi responsible for invasive infections. P. jirovecii is transmitted through the air between healthy individuals, who are considered to be the natural reservoir, at least transiently. In immunocompromised patients, P. jirovecii multiplies, leading to subacute infections and acute life-threatening pneumonia, called Pneumocystis pneumonia [PCP]. PCP is caused by genotypically distinct mixtures of organisms in more than 90% of cases, reinforcing the hypothesis that there is constant inhalation of P. jirovecii from different contacts over time, although reactivation of latent organisms from previous exposures may be possible. Detection of P. jirovecii DNA without any symptoms or related radiological signs has been called "colonization". This situation could be considered as the result of recent exposure to P. jirovecii that could evolve towards PCP, raising the issue of cotrimoxazole prophylaxis for at-risk quantitative polymerase chain reaction (qPCR)-positive immunocompromised patients. The more accurate way to diagnose PCP is the use of real-time quantitative PCR, which prevents amplicon contamination and allows determination of the fungal load that is mandatory to interpret the qPCR results and manage the patient appropriately. The detection of P. jirovecii in respiratory samples of immunocompromised patients should be considered for potential risk of developing PCP. Many challenges still need to be addressed, including a better description of transmission, characterization of organisms present at low level, and prevention of environmental exposure during immunodepression.

Keywords: PCP; Pneumocystis jirovecii; Pneumocystis pneumonia; fungal infections.

Figure 1.. The variable evolution of Pneumocystis fungal load after exposure depending on the host’s immune status.

Upon exposure, P. jirovecii multiplies at the surface of type I pneumocytes in the alveoli. At the very beginning of the infection, quantitative polymerase chain reaction (qPCR) may not be positive owing to very low or localized multiplication of P. jirovecii, even if a bronchoalveolar lavage (the most sensitive specimen) is performed. Depending on the host’s immune status, the evolution of the fungal load could differ: - Rapid and constant multiplication of P. jirovecii leading to Pneumocystis pneumonia (PCP) is typically observed in HIV patients or in patients under immunosuppressive regimens (regular line). The situation known as “PCP” is observed when a high fungal load is associated with symptoms. Note that symptoms appear for lower fungal loads in non-HIV patients compared to HIV patients. - Variable fungal load above or below the detection’s threshold is observed in patients with variable immune status with PCP occurring when immunosuppression increases. This situation is typically seen in hematology or cancer patients submitted to several courses of chemotherapy (dashed line). PCR detection in asymptomatic patients in the situation known as “colonization” could correspond to patients controlling the disease (decreasing fungal load) or to patients who will develop PCP in the near future. The threshold between PCP and “colonization” may be different in HIV-positive and HIV-negative patients. - Immunocompetent patients are potentially a reservoir of P. jirovecii with low multiplication rate due to rapid immune control and subsequent decrease of fungal load. Re-infection with a new genotype or reactivation could occur later on (dotted line).