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Although the incidence of Pneumocystis pneumonia (PCP) has decreased since the introduction of combination antiretroviral therapy, it remains an important cause of disease in both HIV-infected and non-HIV-infected immunosuppressed populations. The epidemiology of PCP has shifted over the course of the HIV epidemic both from changes in HIV and PCP treatment and prevention and from changes in critical care medicine. Although less common in non-HIV-infected immunosuppressed patients, PCP is now more frequently seen due to the increasing numbers of organ transplants and development of novel immunotherapies. New diagnostic and treatment modalities are under investigation. The immune response is critical in preventing this disease but also results in lung damage, and future work may offer potential areas for vaccine development or immunomodulatory therapy. Colonization with Pneumocystis is an area of increasing clinical and research interest and may be important in development of lung diseases such as chronic obstructive pulmonary disease. In this review, we discuss current clinical and research topics in the study of Pneumocystis and highlight areas for future research.

Pneumocystis jirovecii, the fungal agent that causes Pneumocystis pneumonia (PCP), is known to exclusively infect humans. Molecular studies have enabled detection of this fungus in individuals who have been colonized by P. jirovecii. Such colonization, found in several populations, seems to act as a human reservoir for the fungus. Various studies have reported mutations associated with sulfa resistance in P. jirovecii strains isolated from colonized patients, who can transmit the mutant genotype to PCP-susceptible individuals. The growing interest in P. jirovecii colonization may prompt the design of new prevention and management strategies for PCP., (Copyright 2008 Elsevier España, S.L. All rights reserved.)

Background: Prophylaxis against Pneumocystis jiroveci pneumonia (PCP) is only recommended during some periods after renal transplantation. Recent advances in immunosuppressive therapy have considerably reduced acute rejection. However, the reported PCP outbreaks are increasing in renal transplant recipients., Methods: Only three sporadic PCP cases had occurred since 1976 in our Renal Transplant Unit until the index case in July 2004. A PCP outbreak of 27 cases occurred mainly in the outpatient clinic within 1 year, followed by six additional cases during the next 3 years. Molecular analysis of P. jiroveci and surveys of reservoir were performed., Results: Molecular analysis documented that all cases were caused by the same strain. Among 27 cases of the outbreak, human-to-human transmissions were traceable in 22 cases based on dates of outpatient clinic visits and in four cases during hospitalization. Based on the confirmed cases, airborne transmission was suspected with an estimated median PCP incubation period of 53 days (range 7-188 days). Surveys for reservoir of P. jiroveci identified asymptomatic carriers and environmental contamination. Some sporadic cases might be caused by reservoirs. Among the 33 cases, none had received PCP prophylaxis, 22 cases had PCP over 12 months, and six cases over 10 years after renal transplantation., Conclusion: On documentation of a PCP case, we recommend PCP prophylaxis for a maximum period of 6 months (upper limit of incubation period) in all renal transplant recipients including those on regular maintenance immunosuppressive therapy.

We report a case of Pneumocystis jirovecii transmission from colonized grandparents to their infant granddaughter. Genotyping of P. jirovecii showed the same genotypes in samples from the infant and her grandparents. These findings support P. jirovecii transmission from immunocompetent carrier adults to a susceptible child.

The possible presence of Pneumocystis among healthy adults was examined by detecting Pneumocystis jirovecii-specific DNA in prospectively obtained oropharyngeal wash samples from 50 persons without underlying lung disease or immunosuppression. Pneumocystis carriage, defined by detecting Pneumocystis DNA by nested polymerase chain reaction in 2 independent analyses plus successful mitochondrial large subunit ribosomal RNA typing by direct sequencing, was found in 20% of cases. All carriers were asymptomatic, anti-HIV negative, and had normal total lymphocyte and CD4+ cell counts. A second sample obtained in the 6-month follow-up was positive in 2 of 9 available carriers. Genotype analysis showed different polymorphisms; 85A/248C (40%) and 85C/248C (30%) were most frequently observed. This study provides the first evidence that P. jirovecii DNA can be frequently detected in the respiratory tract of immunocompetent adults, which agrees with the hypothesis that the general population could be a reservoir and source of this infection.

The present study was conducted to further examine recent data suggesting that pneumocystosis could be transmitted between patients and healthcare workers in the hospital environment, as has been proven with Pneumocystis-infected SCID mice and immunocompetent Balb/c mice. Using an experimental design (i.e., SCID-Balb/c mouse airborne transmission system), the present work found that healthy host-to-healthy host transmission of Pneumocystis organisms can occur, and that 'second' healthy contacts are able to transmit the infectious organisms to immunocompromised hosts. Further tests designed to explore the behavior of Pneumocystis organisms in the lungs of immunocompetent hosts were performed using histological and molecular approaches (e.g. testing the expression of both cyclin-dependent serine-threonine kinase and heat-shock 70 protein in Pneumocystis). The results showed Pneumocystis organisms were able to replicate in the lungs of immunocompetent hosts, which indicates these hosts are a reservoir for Pneumocystis spp.

Pneumocystis carinii organisms constitute a large group of heterogeneous atypical microscopic fungi that are able to infect immunocompromised mammals by an airborne route and to proliferate in their lungs, inducing Pneumocystis carinii pneumonia. This pneumonia remains a crucial epidemiological challenge, since neither the source of Pneumocystis carinii infection in humans nor the process by which humans become infected has been clearly established. Polymerase chain reaction (PCR) assays have shown that profoundly immunosuppressed patients without pneumocystosis can be subclinically infected with Pneumocystis. Other PCR-based studies have suggested that healthy immunocompetent hosts are not latent carriers of the parasite. However, recent reports have indicated that Pneumocystis carinii can persist for limited periods in the lungs of convalescent rats after recovery from corticosteroid-induced pneumocystosis, and also that immunocompetent mammals can be transiently parasitized by Pneumocystis carinii after close contact with hosts with Pneumocystis carinii pneumonia. Can transiently parasitized hosts be a source of infection for immunosuppressed hosts? In order to investigate this important clinical question, the ability of immunocompetent BALB/c mice, which were carrying subclinical levels of Pneumocystis carinii, to transmit the infection by the airborne route to highly susceptible, uninfected mice with severe combined immunodeficiency was studied. The results indicated that the immunocompetent mice, transiently parasitized by Pneumocystis carinii organisms after close contact with Pneumocystis carinii-infected mice, were able to transmit the infection to Pneumocystis carinii-free mice with severe combined immunodeficiency.

Clusters of Pneumocystis carinii pneumonia (PCP) in immunocompromised settings suggest person-to-person transmission. We examined whether personnel in a ward for HIV-infected patients were carriers of P. carinii. None of 29 sputum samples from 19 personnel caring for HIV-infected patients had detectable amounts of P. carinii DNA, as determined by the two PCR methods used. Two of 26 personnel were found, by an immunofluorescence assay, to have serum antibodies for P. carinii. The results do not support the hypothesis that personnel represent major vectors or transient reservoirs for spreading P. carinii infection to immunocompromised hosts.