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Enrique Calderón - One of the best experts on this subject based on the ideXlab platform.
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Diagnosis, Burden and Mortality of Pneumocystis Jirovecii Pneumonia in Venezuela
Current Fungal Infection Reports, 2020Co-Authors: María Mercedes Panizo, Nataly García, Xiomara Moreno, Trina Navas, Giuseppe Ferrara, Enrique CalderónAbstract:Purpose of the Review The aim of this work is to contribute to the knowledge of diagnosis, burden, and mortality of pneumocystosis or Pneumocystis Jirovecii pneumonia (PCP) in Venezuela. Recent Findings Historically, PCP diagnosis has been clinical and histopathological, but diagnosis based on PCP clinical suspicion, without confirmation of laboratory detection of P. Jirovecii , causes a significant negative impact on both morbidity and mortality of this disease. Risk estimation for PCP and mortality rates according to official records contrasts with the scarce epidemiological data and makes more difficult to have a real view of the impact of this disease in our country. Summary This review summarizes three fundamental aspects: the meaning and usefulness of direct immunofluorescence assay (DIF) and nested PCR (nPCR) for PCP diagnosis in a developing country, risk estimation for PCP based on available national publications, and official mortality rates.
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Epidemiology of Pneumocystis Jirovecii Pneumonia in Venezuela
Current Fungal Infection Reports, 2020Co-Authors: María Mercedes Panizo, Nataly García, Xiomara Moreno, Trina Navas, Giuseppe Ferrara, Enrique CalderónAbstract:Purpose of the Review The aim of this work is to contribute to the knowledge of the epidemiology of pneumocystosis or Pneumocystis Jirovecii pneumonia (PCP) in Venezuela, by an updated review of the information currently available. Recent Findings The PCP epidemiology in Venezuela is not formally known. There is no national surveillance program for mycosis, and systemic mycoses are not mandatory notification diseases. Efforts made to record the disease in our country have not been sufficient; therefore, there is a sub-registry. All the information carried out prevents comparisons with other reports due to the variations in study designs, heterogeneity of the studied patients, and diagnostic methods. Summary This review summarizes the current knowledge about PCP epidemiology in Venezuela based on available national publications. The contributions of these studies are very valuable, since they reflect the need for systematic PCP study, not only in AIDS patients, but in cancer and COPD patients.
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early acquisition of Pneumocystis Jirovecii colonization and potential association with respiratory distress syndrome in preterm newborn infants
Clinical Infectious Diseases, 2017Co-Authors: Pilar Rojas, Enrique Calderón, Carmen De La ,horra, Vicente Friaza, Elisa Garcia, Sergio L Vargas, Antonio PavonAbstract:Background Pneumocystis pneumonia is a well-recognized lung disease of premature and malnourished babies. Even though serologic studies have shown that children are exposed to Pneumocystis Jirovecii early in life, the epidemiology of human P. Jirovecii infection and the host-microorganism relationship in infancy remain poorly understood. The aim of the present study was to investigate the prevalence of P. Jirovecii colonization in preterm infants and its possible association with medical complications. Methods A prospective observational study of preterm infants (birth weight <1500 g and/or gestational age <32 weeks) was carried out. Identification of P. Jirovecii colonization was performed by means of molecular techniques in nasal aspirated samples at birth. Results A total of 128 preterm infants were included during the study period. Pneumocystis DNA was identified in 25.7% (95% confidence interval [CI], 17.8%-33.7%) of newborns studied. A significant increase of respiratory distress syndrome in colonized group, even after adjusting for confounding factors (odds ratio, 2.7 [95% CI, 1.0-7.5]; P = .04), was observed. No differences were observed in other medical conditions between the 2 groups. Conclusions Pneumocystis Jirovecii colonization is frequent in preterm births and could be a risk factor to develop respiratory distress syndrome among preterm infants.
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Diversity of Pneumocystis Jirovecii Across Europe: A Multicentre Observational Study
EBioMedicine, 2017Co-Authors: Alexandre Alanio, Enrique Calderón, Maud Gits-muselli, Nicolas Guigue, Marie Desnos-ollivier, David Di Cave, Damien Dupont, Axel Hamprecht, Philippe Hauser, Jannik Helweg-larsenAbstract:Pneumocystis Jirovecii is an airborne human-specific ascomycetous fungus responsible for Pneumocystis pneumonia (PCP) in immunocompromised patients, affecting >500,000 patients per year (www.gaffi.org). The understanding of its epidemiology is limited by the lack of standardised culture. Recent genotyping data suggests a limited genetic diversity of P. Jirovecii. The objective of the study was to assess the diversity of P. Jirovecii across European hospitals and analyse P. Jirovecii diversity in respect to clinical data obtained from the patients. Genotyping was performed using six already validated short tandem repeat (STR) markers on 249 samples (median: 17 per centre interquartile range [11-20]) from PCP patients of 16 European centres. Mixtures of STR markers (i.e., ≥2 alleles for ≥1 locus) were detected in 67.6% (interquartile range [61.4; 76.5]) of the samples. Mixture was significantly associated with the underlying disease of the patient, with an increased proportion in HIV patients (78.3%) and a decreased proportion in renal transplant recipients (33.3%) (p
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Pneumocystis Jirovecii pneumonia in latin america a public health problem
Expert Review of Anti-infective Therapy, 2013Co-Authors: Enrique Calderón, María Mercedes Panizo, Yaxsier De Armas, Gustavo WissmannAbstract:Pneumocystis Jirovecii pneumonia (PcP) is a well-recognized major opportunistic infection in HIV-infected patients. During the 1980s, the HIV pandemic turned PcP into a major worldwide medical and public health problem. With the introduction of Pneumocystis chemoprophylaxis and the development of highly active antiretroviral therapy (ART) for the treatment of HIV infection, there has been a decrease in PcP incidence in developed countries. However, the prevalence of AIDS-related PcP in developing countries remains high because a lot of people do not have access to ART or ignore their HIV infection status. This article discusses the information available about PcP among Latin American countries where there is a great regional heterogeneity in the prevalence of HIV infection and in ART coverage, as well as in the observed frequencies of PcP that range from 5.9 to 55% in this area.
Joseph A. Kovacs - One of the best experts on this subject based on the ideXlab platform.
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humans are selectively exposed to Pneumocystis Jirovecii
Mbio, 2020Co-Authors: Ousmane H Cisse, Chao Jiang, Michael Snyder, Joseph A. KovacsAbstract:Environmental exposure has a significant impact on human health. While some airborne fungi can cause life-threatening infections, the impact of environment on fungal spore dispersal and transmission is poorly understood. The democratization of shotgun metagenomics allows us to explore important questions about fungal propagation. We focus on Pneumocystis, a genus of host-specific fungi that infect mammals via airborne particles. In humans, Pneumocystis Jirovecii causes lethal infections in immunocompromised patients if untreated, although its environmental reservoir and transmission route remain unclear. Here, we attempt to clarify, by analyzing human exposome metagenomic data sets, whether humans are exposed to different Pneumocystis species present in the air but only P. Jirovecii cells are able to replicate or whether they are selectively exposed to P. Jirovecii Our analysis supports the latter hypothesis, which is consistent with a local transmission model. These data also suggest that healthy carriers are a major driver for the transmission.
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Genetic diversity of Pneumocystis Jirovecii from a cluster of cases of pneumonia in renal transplant patients: Cross-sectional study.
Mycoses, 2018Co-Authors: Giannina Ricci, Daniel Wagner De Castro Lima Santos, Joseph A. Kovacs, Angela Satie Nishikaku, Tainá Veras De Sandes-freitas, Anderson Messias Rodrigues, Geetha Kutty, Regina Affonso, Helio Tedesco Silva, José O. Medina-pestanaAbstract:Pneumocystis Jirovecii can cause severe potentially life-threatening pneumonia (PCP) in kidney transplant patients. Prophylaxis of patients against PCP in this setting is usually performed during 6 months after transplantation. The aim of this study is to describe the molecular epidemiology of a cluster of PCP in renal transplant recipients in Brazil. Renal transplant patients who developed PCP between May and December 2011 had their formalin-fixed paraffin-embedded (FFPE) lung biopsy samples analysed. Pneumocystis Jirovecii 23S mitochondrial large subunit of ribosomal RNA (23S mtLSU-rRNA), 26S rRNA, and dihydropteroate synthase (DHPS) genes were amplified by polymerase chain reaction (PCR), sequenced, and analysed for genetic variation. During the study period, 17 patients developed PCP (only four infections were documented within the first year after transplantation) and six (35.3%) died. Thirty FFPE samples from 11 patients, including one external control HIV-infected patient, had fungal DNA successfully extracted for further amplification and sequencing for all three genes. A total of five genotypes were identified among the 10 infected patients. Of note, four patients were infected by more than one genotype and seven patients were infected by the same genotype. DNA extracted from FFPE samples can be used for genotyping; this approach allowed us to demonstrate that multiple P. Jirovecii strains were responsible for this cluster, and one genotype was found infecting seven patients. The knowledge of the causative agents of PCP may help to develop new initiatives for control and prevention of PCP among patients undergoing renal transplant and improve routine PCP prophylaxis.
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outbreak of Pneumocystis pneumonia in renal and liver transplant patients caused by genotypically distinct strains of Pneumocystis Jirovecii
Transplantation, 2013Co-Authors: Andreas A Rostved, Geetha Kutty, Monica Sassi, Jorgen A L Kurtzhals, Soren Schwartz Sorensen, Allan Rasmussen, Christian Ross, Emile Gogineni, Charles Huber, Joseph A. KovacsAbstract:Background An outbreak of 29 cases of Pneumocystis Jirovecii pneumonia (PCP) occurred among renal and liver transplant recipients (RTR and LTR) in the largest Danish transplantation centre between 2007 and 2010, when routine PCP prophylaxis was not used.
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Expression of Pneumocystis Jirovecii Major Surface Glycoprotein in Saccharomyces cerevisiae
The Journal of infectious diseases, 2013Co-Authors: Geetha Kutty, Katherine J. England, Joseph A. KovacsAbstract:The major surface glycoprotein (Msg), which is the most abundant protein expressed on the cell surface of Pneumocystis organisms, plays an important role in the attachment of this organism to epithelial cells and macrophages. In the present study, we expressed Pneumocystis Jirovecii Msg in Saccharomyces cerevisiae, a phylogenetically related organism. Full-length P. Jirovecii Msg was expressed with a DNA construct that used codons optimized for expression in yeast. Unlike in Pneumocystis organisms, recombinant Msg localized to the plasma membrane of yeast rather than to the cell wall. Msg expression was targeted to the yeast cell wall by replacing its signal peptide, serine-threonine–rich region, and glycophosphatidylinositol anchor signal region with the signal peptide of cell wall protein α-agglutinin of S. cerevisiae, the serine-threonine–rich region of epithelial adhesin (Epa1) of Candida glabrata, and the carboxyl region of the cell wall protein (Cwp2) of S. cerevisiae, respectively. Immunofluorescence analysis and treatment with β-1,3 glucanase demonstrated that the expressed Msg fusion protein localized to the yeast cell wall. Surface expression of Msg protein resulted in increased adherence of yeast to A549 alveolar epithelial cells. Heterologous expression of Msg in yeast will facilitate studies of the biologic properties of Pneumocystis Msg.
Philippe M. Hauser - One of the best experts on this subject based on the ideXlab platform.
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Expression pattern of the Pneumocystis Jirovecii major surface glycoprotein superfamily in patients with pneumonia.
The Journal of infectious diseases, 2020Co-Authors: Emanuel Schmid-siegert, Sophie Richard, Amanda Luraschi, Konrad Mühlethaler, Marco Pagni, Philippe M. HauserAbstract:BACKGROUND The human pathogen Pneumocystis Jirovecii harbors six families of major surface glycoproteins (MSG) encoded by a single gene superfamily. MSGs are presumably responsible for antigenic variation and adhesion to host cells. The genomic organization suggests that a single member of family I is expressed at a time per cell, whereas members of the other families are simultaneously expressed. METHODS We analyzed RNA sequences expressed in several clinical samples, using specific weighted profiles for reads sorting and single nucleotide variants calling to estimate the diversity of the expressed genes. RESULTS A number of different isoforms of at least four MSG families were expressed simultaneously, including of family I for which confirmation was obtained in the wet laboratory. CONCLUSION These observations suggest that every single P. Jirovecii population is made of individual cells with distinct surface properties. Our results enhance our understanding of the unique antigenic variation system and cell surface structure of P. Jirovecii.
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Pneumocystis Jirovecii genotype associated with increased death rate of HIV-infected patients with pneumonia.
Emerging Infectious Diseases, 2013Co-Authors: Meja Rabodonirina, Laetitia Vaillant, Patrick Taffé, Aimable Nahimana, René-pierre Gillibert, Philippe Vanhems, Philippe M. HauserAbstract:Pneumocystis Jirovecii dihydropteroate synthase (DHPS) mutations have been associated with failure of sulfa prophylaxis; their effect on the outcome of patients with P. Jirovecii pneumonia (PCP) remains controversial. P. Jirovecii DHPS polymorphisms and genotypes were identified in 112 cases of PCP in 110 HIV-infected patients by using PCR single-strand conformation polymorphism. Of the 110 patients observed, 21 died; 18 of those deaths were attributed to PCP. Thirty-three percent of the PCP cases involved a P. Jirovecii strain that had 1 or both DHPS mutations. The presence or absence of DHPS mutations had no effect on the PCP mortality rate within 1 month, whereas P.Jirovecii type 7 and mechanical ventilation at PCP diagnosis were associated with an increased risk of death caused by PCP. Mechanical ventilation at PCP diagnosis was also associated with an increased risk of sulfa treatment failure at 5 days.
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molecular evidence of interhuman transmission in an outbreak of Pneumocystis Jirovecii pneumonia among renal transplant recipients
Transplant Infectious Disease, 2010Co-Authors: Sara Gianella, Philippe M. Hauser, Lea Haeberli, Beda Joos, Bruno Ledergerber, Rudolf P Wuthrich, Rainer Weber, Herbert Kuster, Thomas Fehr, Nicolas J MuellerAbstract:S. Gianella, L. Haeberli, B. Joos, B. Ledergerber, R.P. Wuthrich, R. Weber, H. Kuster, P.M. Hauser, T. Fehr, N.J. Mueller. Molecular evidence of interhuman transmission in an outbreak of Pneumocystis Jirovecii pneumonia among renal transplant recipients. Transpl Infect Dis 2010: 12: 1–10. All rights reserved Abstract: Pneumocystis Jirovecii pneumonia (PCP) remains an important cause of morbidity and mortality in immunocompromised individuals. The epidemiology and pathogenesis of this infection are poorly understood, and the exact mode of transmission remains unclear. Recent studies reported clusters of PCP among immunocompromised patients, raising the suspicion of interhuman transmission. An unexpected increase of the incidence of PCP cases in our nephrology outpatient clinic prompted us to conduct a detailed analysis. Genotyping of 7 available specimens obtained from renal transplant recipients was performed using multi-locus DNA sequence typing (MLST). Fragments of 4 variable regions of the P. Jirovecii genome (ITS1, 26S, mt26S, β-tubulin) were sequenced and compared with those of 4 independent control patients. MLST analysis revealed identical sequences of the 4 regions among all 7 renal allograft recipients with available samples, indicating an infection with the same P. Jirovecii genotype. We observed that all but 1 of the 19 PCP-infected transplant recipients had at least 1 concomitant visit with another PCP-infected patient within a common waiting area. This study provides evidence that nosocomial transmission among immunocompromised patients may have occurred in our nephrology outpatient clinic. Our findings have epidemiological implications and suggest that prolonged chemoprophylaxis for PCP may be warranted in an era of more intense immunosuppression.
Geetha Kutty - One of the best experts on this subject based on the ideXlab platform.
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Genetic diversity of Pneumocystis Jirovecii from a cluster of cases of pneumonia in renal transplant patients: Cross-sectional study.
Mycoses, 2018Co-Authors: Giannina Ricci, Daniel Wagner De Castro Lima Santos, Joseph A. Kovacs, Angela Satie Nishikaku, Tainá Veras De Sandes-freitas, Anderson Messias Rodrigues, Geetha Kutty, Regina Affonso, Helio Tedesco Silva, José O. Medina-pestanaAbstract:Pneumocystis Jirovecii can cause severe potentially life-threatening pneumonia (PCP) in kidney transplant patients. Prophylaxis of patients against PCP in this setting is usually performed during 6 months after transplantation. The aim of this study is to describe the molecular epidemiology of a cluster of PCP in renal transplant recipients in Brazil. Renal transplant patients who developed PCP between May and December 2011 had their formalin-fixed paraffin-embedded (FFPE) lung biopsy samples analysed. Pneumocystis Jirovecii 23S mitochondrial large subunit of ribosomal RNA (23S mtLSU-rRNA), 26S rRNA, and dihydropteroate synthase (DHPS) genes were amplified by polymerase chain reaction (PCR), sequenced, and analysed for genetic variation. During the study period, 17 patients developed PCP (only four infections were documented within the first year after transplantation) and six (35.3%) died. Thirty FFPE samples from 11 patients, including one external control HIV-infected patient, had fungal DNA successfully extracted for further amplification and sequencing for all three genes. A total of five genotypes were identified among the 10 infected patients. Of note, four patients were infected by more than one genotype and seven patients were infected by the same genotype. DNA extracted from FFPE samples can be used for genotyping; this approach allowed us to demonstrate that multiple P. Jirovecii strains were responsible for this cluster, and one genotype was found infecting seven patients. The knowledge of the causative agents of PCP may help to develop new initiatives for control and prevention of PCP among patients undergoing renal transplant and improve routine PCP prophylaxis.
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outbreak of Pneumocystis pneumonia in renal and liver transplant patients caused by genotypically distinct strains of Pneumocystis Jirovecii
Transplantation, 2013Co-Authors: Andreas A Rostved, Geetha Kutty, Monica Sassi, Jorgen A L Kurtzhals, Soren Schwartz Sorensen, Allan Rasmussen, Christian Ross, Emile Gogineni, Charles Huber, Joseph A. KovacsAbstract:Background An outbreak of 29 cases of Pneumocystis Jirovecii pneumonia (PCP) occurred among renal and liver transplant recipients (RTR and LTR) in the largest Danish transplantation centre between 2007 and 2010, when routine PCP prophylaxis was not used.
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Expression of Pneumocystis Jirovecii Major Surface Glycoprotein in Saccharomyces cerevisiae
The Journal of infectious diseases, 2013Co-Authors: Geetha Kutty, Katherine J. England, Joseph A. KovacsAbstract:The major surface glycoprotein (Msg), which is the most abundant protein expressed on the cell surface of Pneumocystis organisms, plays an important role in the attachment of this organism to epithelial cells and macrophages. In the present study, we expressed Pneumocystis Jirovecii Msg in Saccharomyces cerevisiae, a phylogenetically related organism. Full-length P. Jirovecii Msg was expressed with a DNA construct that used codons optimized for expression in yeast. Unlike in Pneumocystis organisms, recombinant Msg localized to the plasma membrane of yeast rather than to the cell wall. Msg expression was targeted to the yeast cell wall by replacing its signal peptide, serine-threonine–rich region, and glycophosphatidylinositol anchor signal region with the signal peptide of cell wall protein α-agglutinin of S. cerevisiae, the serine-threonine–rich region of epithelial adhesin (Epa1) of Candida glabrata, and the carboxyl region of the cell wall protein (Cwp2) of S. cerevisiae, respectively. Immunofluorescence analysis and treatment with β-1,3 glucanase demonstrated that the expressed Msg fusion protein localized to the yeast cell wall. Surface expression of Msg protein resulted in increased adherence of yeast to A549 alveolar epithelial cells. Heterologous expression of Msg in yeast will facilitate studies of the biologic properties of Pneumocystis Msg.
Sandrine Valade - One of the best experts on this subject based on the ideXlab platform.
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Diffusion of Pneumocystis Jirovecii in the surrounding air of patients with Pneumocystis colonization: frequency and putative risk factors: Table 1.
Medical Mycology, 2017Co-Authors: Emilie Fréalle, Anne Totet, Sandrine Valade, Samia Hamane, Nicolas Guigue, Céline Damiani, Magali Chabé, Solène Le gal, El Moukhtar Aliouat, Gilles NevezAbstract:In a prospective bicentric study, Pneumocystis Jirovecii excretion and diffusion was explored in air samples collected in the rooms occupied by 17 Pneumocystis-colonized patients. P. Jirovecii DNA was detected by real-time PCR in the air collected from 3 patients' rooms (17.6%), with identical genotypes in corresponding clinical and air samples. Pneumocystis DNA was detected for 2/3 patients with autoimmune disease treated with corticosteroids versus 1/6 patients with hematologic disease and 0/5 kidney transplant recipients. These data confirm the possible excretion of the fungus by Pneumocystis-colonized patients and thus bring additional arguments for the prevention of airborne transmission in hospital wards.
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New Short Tandem Repeat-Based Molecular Typing Method for Pneumocystis Jirovecii Reveals Intrahospital Transmission between Patients from Different Wards
PLoS ONE, 2015Co-Authors: Maud Gits-muselli, Samia Hamane, Nicolas Guigue, Marienoelle Peraldi, Nathalie Castro, Véronique Delcey, Jean Menotti, Emmanuel Raffoux, Anne Bergeron, Sandrine ValadeAbstract:Pneumocystis pneumonia is a severe opportunistic infection in immunocompromised patients caused by the unusual fungus Pneumocystis Jirovecii. Transmission is airborne, with both immunocompromised and immunocompetent individuals acting as a reservoir for the fungus. Numerous reports of outbreaks in renal transplant units demonstrate the need for valid genotyping methods to detect transmission of a given genotype. Here, we developed a short tandem repeat (STR)-based molecular typing method for P. Jirovecii. We analyzed the P. Jirovecii genome and selected six genomic STR markers located on different contigs of the genome. We then tested these markers in 106 P. Jirovecii PCR-positive respiratory samples collected between October 2010 and November 2013 from 91 patients with various underlying medical conditions. Unique (one allele per marker) and multiple (more than one allele per marker) genotypes were observed in 34 (32%) and 72 (68%) samples, respectively. A genotype could be assigned to 55 samples (54 patients) and 61 different genotypes were identified in total with a discriminatory power of 0.992. Analysis of the allelic distribution of the six markers and minimum spanning tree analysis of the 61 genotypes identified a specific genotype (Gt21) in our hospital, which may have been transmitted between 10 patients including six renal transplant recipients. Our STR-based molecular typing method is a quick, cheap and reliable approach to genotype Pneumocystis Jirovecii in hospital settings and is sensitive enough to detect minor genotypes, thus enabling the study of the transmission and pathophysiology of Pneumocystis pneumonia.
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Pneumocystis Jirovecii Pneumonia in Patients with or without AIDS, France
Emerging Infectious Diseases, 2014Co-Authors: Antoine Roux, Danièle Maubon, Emmanuel Canet, Sandrine Valade, Florence Gangneux-robert, Samia Hamane, Ariane Lafabrie, Anne Debourgogne, Soléne Le Gal, Fréderic DalleAbstract:Pneumocystis Jirovecii pneumonia (PCP) in patients without AIDS is increasingly common. We conducted a prospective cohort study of consecutive patients with proven PCP; of 544 patients, 223 (41%) had AIDS (AIDS patients) and 321 (59%) had other immunosuppressive disorders (non-AIDS patients). Fewer AIDS than non-AIDS patients required intensive care or ventilation, and the rate of hospital deaths—17.4% overall—was significantly lower for AIDS versus non-AIDS patients (4% vs. 27%; p
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Pneumocystis Jirovecii pneumonia in patients with or without aids france
Emerging Infectious Diseases, 2014Co-Authors: Antoine Roux, Danièle Maubon, Emmanuel Canet, Sandrine Valade, Samia Hamane, Ariane Lafabrie, Anne Debourgogne, Florence Gangneuxrobert, Solene Le Gal, Fréderic DalleAbstract:Pneumocystis Jirovecii pneumonia (PCP) in patients without AIDS is increasingly common. We conducted a prospective cohort study of consecutive patients with proven PCP; of 544 patients, 223 (41%) had AIDS (AIDS patients) and 321 (59%) had other immunosuppressive disorders (non-AIDS patients). Fewer AIDS than non-AIDS patients required intensive care or ventilation, and the rate of hospital deaths—17.4% overall—was significantly lower for AIDS versus non-AIDS patients (4% vs. 27%; p<0.0001). Multivariable analysis showed the odds of hospital death increased with older age, receipt of allogeneic bone marrow transplant, immediate use of oxygen, need for mechanical ventilation, and longer time to treatment; HIV-positive status or receipt of a solid organ transplant decreased odds for death. PCP is more often fatal in non-AIDS patients, but time to diagnosis affects survival and is longer for non-AIDS patients. Clinicians must maintain a high index of suspicion for PCP in immunocompromised patients who do not have AIDS.