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Pneumocystis jirovecii Pneumonia: Epidemiology, Clinical Manifestation and Diagnosis

  • P. Lewis WhiteEmail author
  • Jessica S. Price
  • Matthijs Backx
Clinical Pathology (S Challa, Section Editor)
  • 3 Downloads
Part of the following topical collections:
  1. Topical Collection on Clinical Pathology

Abstract

Purpose of Review

The purpose of this study is to provide an understanding of the increased range of patient cohorts at risk of Pneumocystis jirovecii pneumonia (PCP) and describe typical clinical presentations together with advances in diagnostic assays and strategies.

Recent Findings

The range of immuno-compromised patients at risk of PCP continues to expand. Apart from human immunodeficiency virus (HIV)-positive patients, those with solid tumours or suffering from haematological malignancy, solid organ transplant recipients or with autoimmune and inflammatory conditions receiving immuno-modulating therapies and patients diagnosed with primary immune deficiencies are all at increased risk of PCP. The clinical presentation of respiratory distress may be mild/moderate in the HIV-positive patient, but fulminant in HIV-negative. While typical clinical signs of PCP, along with underlying risk factors and the absence of alternative diagnoses, may be sufficient to commence therapy, every effort should be made to achieve a mycological diagnosis. With the advent of modern diagnostics techniques (real-time polymerase chain reaction (PCR) and (1-3)-β-D-Glucan), a laboratory-based diagnosis should always be attempted, although microscopic identification of Pneumocystis within respiratory samples remains the reference method. By combining different assays, it may be possible to both exclude and confirm PCP, without the need for invasive samples.

Summary

This review will summarize the epidemiology, clinical manifestations and diagnostic options for PCP, and also briefly cover therapeutic management, the emerging issue of resistance and PCP in paediatric age group.

Keywords

Pneumocystis PCP Diagnosis Epidemiology Clinical presentation 

Notes

Compliance with Ethical Standards

Conflict of Interest

P. Lewis White served on an advisory board for F2G and Gilead; received speakers’ honoraria from Gilead, MSD and BOPA; received funding for travel and meeting attendance from Gilead, Launch Diagnostics, BOPA and Bruker Diagnostics; received research funding from Bruker Diagnostics; received payment from F2G for providing diagnostic services and is a founding member of the European Aspergillus PCR initiative. Jessica Price and Matthijs Backx declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Maini R, Henderson KL, Sheridan EA, Lamagni T, Nichols G, Delpech V, et al. Increasing Pneumocystis pneumonia, England, UK, 2000–2010. Emerg Infect Dis. 2013;19(3):386–92.  https://doi.org/10.3201/eid1903.121151.Google Scholar
  2. 2.
    Patterson L, Coyle P, Curran T, Verlander NQ, Johnston J. Changing epidemiology of Pneumocystis pneumonia, Northern Ireland, UK and implications for prevention, 1 July 2011–31 July 2012. J Med Microbiol. 2017;66:1650–165.  https://doi.org/10.1099/jmm.0.000617.Google Scholar
  3. 3.
    Pegorie M, Denning DW, Welfare W. Estimating the burden of invasive and serious fungal disease in the United Kingdom. J Inf Secur. 2016.  https://doi.org/10.1016/j.jinf.2016.10.005.
  4. 4.
    Buchacz K, Lau B, Jing Y, Bosch R, Abraham AG, et al. Incidence of AIDS-defining opportunistic infections in a multicohort analysis of HIV-infected persons in the United States and Canada, 2000–2010. J Infect Dis. 2016;214:862–72.  https://doi.org/10.1093/infdis/jiw085.Google Scholar
  5. 5.
    Williams KM, Ahn KW, Chen M, Aljurf MD, Agwu AL, et al. The incidence, mortality and timing of Pneumocystis jiroveci pneumonia after hematopoietic cell transplantation: a CIBMTR analysis. Bone Marrow Transplant. 2016;51:573–80.  https://doi.org/10.1038/bmt.2015.316.Google Scholar
  6. 6.
    Avino LJ, Naylor SM, Roecker AM. Pneumocystis jirovecii pneumonia in the non-HIV infected population. Ann Pharmacother. 2016;50:673–9.  https://doi.org/10.1177/1060028016650107.Google Scholar
  7. 7.
    Iriat X, Challan Belval T, Fillaux J, et al. Risk factors of Pneumocystis pneumonia in solid organ transplant recipients in the era of the common use of posttransplantation prophylaxis. Am J Transplant. 2015;15:190–9.  https://doi.org/10.1111/ajt.12947.Google Scholar
  8. 8.
    Montesinos I, Delforge ML, Ajjaham F, Brancart F, Hites M, Jacobs F, et al. Evaluation of a new commercial real-time PCR assay for diagnosis of Pneumocystis jirovecii pneumonia and identification of dihydropteroate synthase (DHPS) mutations. Diagn Microbiol Infect Dis. 2017;87(1):32–6.  https://doi.org/10.1016/j.diagmicrobio.2016.10.005.Google Scholar
  9. 9.
    Hay J, Osmond D, Jacobson M. Projecting the medical costs of AIDS and ARC in the United States. J Aquir Immune Defic Syndr. 1988;1(5):466–85.Google Scholar
  10. 10.
    Salzer HJF, Schäfer G, Hoenigl M, Günther G, Hoffmann C, Kalsdorf B, et al. Clinical, diagnostic, and treatment disparities between HIV-infected and non-HIV-infected immunocompromised patients with Pneumocystis jirovecii pneumonia. Respiration. 2018;96(1):52–65.  https://doi.org/10.1159/000487713.Google Scholar
  11. 11.
    Oladele R, Otu A, Richardson M, Denning D. Diagnosis and management of Pneumocystis pneumonia in resource-poor settings. J Health Care Poor Undeserved. 2018;29(1):107–58.  https://doi.org/10.1353/hpu.2018.0010.Google Scholar
  12. 12.
    Lee HY, Choi SH, Kim T, Chang J, Kim SH, Lee SO, et al. Epidemiologic trends and clinical features of Pneumocystis jirovecii pneumonia in non-HIV patients in a tertiary-care hospital in Korea over a 15-year-period. Jpn J Infect Dis. 2019.  https://doi.org/10.7883/yoken.JJID.2018.400.
  13. 13.
    Wolfe RM, Peacock JE Jr. Pneumocystis pneumonia and the rheumatologist: which patients are at risk and how can PCP be prevented? Curr Rheumatol Rep. 2017;19:35.  https://doi.org/10.1007/s11926-017-0664-6.Google Scholar
  14. 14.
    Alexandre K, Ingen-Housz-Oro S, Versini M, Sailler L, Benhamou Y. Pneumocystis jirovecii pneumonia in patients treated with rituximab for systemic diseases: report of 11 cases and review of the literature. Eur J Intern Med. 2018;50:e23–4.  https://doi.org/10.1016/j.ejim.2017.11.014.Google Scholar
  15. 15.
    Amber K, Lamberts A, Solimani F, Agnoletti A, Didona D, Euverman I, et al. Determining the incidence of Pneumocystis pneumonia in patients with autoimmune blistering diseases not receiving routine prophylaxis. JAMA Dermatol. 2017;153(11):1137.  https://doi.org/10.1001/jamadermatol.2017.2808.Google Scholar
  16. 16.
    Szydłowicz M, Jakuszko K, Szymczak A, Piesiak P, Kowal A, Kopacz Ż, et al. Prevalence and genotyping of Pneumocystis jirovecii in renal transplant recipients—preliminary report. Parasitol Res. 2018;118(1):181–9.  https://doi.org/10.1007/s00436-018-6131-0.Google Scholar
  17. 17.
    Neofytos D, Hirzel C, Boely E, Lecompte T, Khanna N, Mueller N, et al. Pneumocystis jirovecii pneumonia in solid organ transplant recipients: a descriptive analysis for the Swiss Transplant Cohort. Transpl Infect Dis. 2018;20(6):e12984.  https://doi.org/10.1111/tid.12984.Google Scholar
  18. 18.
    Redjoul R, Robin C, Foulet F, Leclerc M, Beckerich F, Cabanne L, et al. Pneumocystis jirovecii pneumonia prophylaxis in allogeneic hematopoietic cell transplant recipients: can we always follow the guidelines? Bone Marrow Transplant. 2018.  https://doi.org/10.1038/s41409-018-0391-2.
  19. 19.
    Maschmeyer G, Helweg-Larsen J, Pagano L, Robin C, Cordonnier C, Schellongowski P. 6th European Conference on Infections in Leukemia (ECIL-6), a joint venture of The European Group for Blood and Marrow Transplantation (EBMT), The European Organization for Research and Treatment of Cancer (EORTC), the International Immunocompromised Host Society (ICHS) and The European LeukemiaNet (ELN). ECIL guidelines for treatment of Pneumocystis jirovecii pneumonia in non-HIV-infected haematology patients. J Antimicrob Chemother. 2016;71(9):2405–13.  https://doi.org/10.1093/jac/dkw158.Google Scholar
  20. 20.
    Shimada K, Yokosuka K, Nunokawa T, Sugii S. Differences in clinical Pneumocystis pneumonia in rheumatoid arthritis and other connective tissue diseases suggesting a rheumatoid-specific interstitial lung injury spectrum. Clin Rheumatol. 2018;37(8):2269–74.  https://doi.org/10.1007/s10067-018-4157-4.Google Scholar
  21. 21.
    Miller RF, Le Noury J, Corbett EL, et al. Pneumocystis carinii infection: current treatment and prevention. J Antimicrob Chemother. 1996;37(Suppl B):33–53.  https://doi.org/10.1093/jac/37.suppl_b.33.Google Scholar
  22. 22.
    White PL, Backx M, Barnes RA. Diagnosis and management of Pneumocystis jirovecii infection. Expert Rev Anti-Infect Ther. 2017;15(5):435–47.  https://doi.org/10.1080/14787210.2017.1305887.Google Scholar
  23. 23.
    Iriart X, Bouar ML, Kamar N, Berry A. Pneumocystis pneumonia in solid-organ transplant recipients. J Fungi (Basel). 2015;1(3):293–331.  https://doi.org/10.3390/jof1030293.Google Scholar
  24. 24.
    Liu Y, Su L, Jiang SJ, Qu H. Risk factors for mortality from Pneumocystis carinii pneumonia (PCP) in non-HIV patients: a meta-analysis. Oncotarget. 2017;8(35):59729–39.  https://doi.org/10.18632/oncotarget.19927.Google Scholar
  25. 25.
    Lee E, Kim E, Lee S, Roh Y, Leem A, Song J, et al. Risk factors and clinical characteristics of Pneumocystis jirovecii pneumonia in lung cancer. Sci Rep. 2019;9(1):2094.  https://doi.org/10.1038/s41598-019-38618-3.Google Scholar
  26. 26.
    Garg N, Jorgenson M, Descourouez J, Saddler C, Parajuli S, Astor B, et al. Pneumocystis jiroveci pneumonia in kidney and simultaneous pancreas kidney transplant recipients in the present era of routine post-transplant prophylaxis: risk factors and outcomes. BMC Nephrol. 2018;19(1):332.  https://doi.org/10.1186/s12882-018-1142-8.Google Scholar
  27. 27.
    Fei MW, Kim EJ, Sant CA, et al. Prediciting mortality from HIV-associated Pneumocystis pneumonia at illness presentation: an observational cohort study. Thorax. 2009;64:1070–6.  https://doi.org/10.1136/thx.2009.117846.Google Scholar
  28. 28.
    Weng L, Huang X, Chen L, Feng LQ, Jiang W, Hu XY, et al. Prognostic factors for severe Pneumocystis jiroveci pneumonia of non-HIV patients in intensive care unit: a bicentric retrospective study. BMC Infect Dis. 2016;16(1):528.  https://doi.org/10.1186/s12879-016-1855-x.Google Scholar
  29. 29.
    Mu X-D, Jia P, Gao L, et al. Relationship between radiological stages and prognoses of Pneumocystis pneumonia in non-AIDS immunocompromised patients. Chin Med J. 2016;129(17):2020–5.  https://doi.org/10.4103/0366-6999.189068.Google Scholar
  30. 30.
    She W, Chok K, Li I, Ma K, Sin S, Dai W, et al. Pneumocystis jirovecii-related spontaneous pneumothorax, pneumomediastinum and subcutaneous emphysema in a liver transplant recipient: a case report. BMC Infect Dis. 2019;19(1):66.  https://doi.org/10.1186/s12879-019-3723-y.Google Scholar
  31. 31.
    Vogel MN, Brodoefel H, Hierl T, Beck R, Bethge WA, Claussen CD, et al. Differences and similarities of cytomegalovirus and Pneumocystis pneumonia in HIV-negative immunocompromised patients thin section CT morphology in the early phase of the disease. Br J Radiol. 2007;80(955):516–23.  https://doi.org/10.1259/bjr/39696316.Google Scholar
  32. 32.
    Hidalgo A, Falcó V, Mauleón S, Andreu J, Crespo M, Ribera E, et al. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non-Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol. 2003;13(5):1179–84.  https://doi.org/10.1007/s00330-002-1641-6.Google Scholar
  33. 33.
    Taeb A, Sill J, Derber C, Hooper M. Nodular granulomatous Pneumocystis jiroveci pneumonia consequent to delayed immune reconstitution inflammatory syndrome. Int J STD AIDS. 2018;29(14):1451–3.  https://doi.org/10.1177/0956462418787603.Google Scholar
  34. 34.
    Tokuda H, Sakai F, Yamada H, Johkoh T, Imamura A, Dohi M, et al. Clinical and radiological features of Pneumocystis pneumonia in patients with rheumatoid arthritis, in comparison with methotrexate pneumonitis and Pneumocystis pneumonia in acquired immunodeficiency syndrome: a multicenter study. Intern Med. 2008;47(10):915–23.  https://doi.org/10.2169/internalmedicine.47.0702.Google Scholar
  35. 35.
    Block B, Mehta T, Ortiz G, Ferris S, Vu T, Huang L, et al. Unusual radiographic presentation of Pneumocystis pneumonia in a patient with AIDS. Case Rep Infect Dis. 2017:3183525.  https://doi.org/10.1155/2017/3183525.
  36. 36.
    • Cereser L, Dallorto A, Candoni A, Volpetti S, Righi E, Zuiani C, et al. Pneumocystis jirovecii pneumonia at chest high-resolution computed tomography (HRCT) in non-HIV immunocompromised patients: spectrum of findings and mimickers. Eur J Radiol. 2019;116:116–27.  https://doi.org/10.1016/j.ejrad.2019.04.025 Excellent summary of the typical PcP chest radiology in HIV-negative, important given the increasing incidence of disease in this cohort. Google Scholar
  37. 37.
    White PL, Price JS, Backx M. Therapy and management of Pneumocystis jirovecii Infection. J Fungi (Basel). 2018;4(4):E127.  https://doi.org/10.3390/jof4040127.Google Scholar
  38. 38.
    Karageorgopoulos DE, Qu JM, Korbila IP, Zhu YG, Vasileiou VA, Falagas ME. Accuracy of b-D-glucan for the diagnosis of Pneumocystis jirovecii pneumonia: a meta-analysis. Clin Microbiol Infect. 2013;19(1):39–49.  https://doi.org/10.1111/j.1469-0691.2011.03760.x.Google Scholar
  39. 39.
    Onishi A, Sugiyama D, Kogata Y, Saegusa J, Sugimoto T, Kawano S, et al. Diagnostic accuracy of serum 1,3-β-D-Glucan for Pneumocystis jiroveci pneumonia, invasive Candidiasis, and invasive Aspergillosis: systematic review and meta-Analysis. J Clin Microbiol. 2012;50(1):7–15.  https://doi.org/10.1128/JCM.05267-11.Google Scholar
  40. 40.
    Li WJ, Guo YL, Liu TJ, Wang K, Kong JL. Diagnosis of pneumocystis pneumonia using serum (1-3)-β-D-Glucan:a bivariate meta-analysis and systematic review. Thorac Dis. 2015;7(12):2214–25.  https://doi.org/10.3978/j.issn.2072-1439.2015.12.27.Google Scholar
  41. 41.
    Summah H, Zhu Y-G, Falagas ME, Vouloumanou EK, Qu J-M. Use of real-time polymerase chain reaction for the diagnosis of Pneumocystis pneumonia in immunocompromised patients: a meta-analysis. Chin Med J. 2013;126:1965–73.Google Scholar
  42. 42.
    Fan L-C, Lu H-W, Cheng K-B, Li H-P, Xu J-F. Evaluation of PCR in bronchoalveolar lavage fluid for diagnosis of Pneumocystis jirovecii pneumonia: a bivariate meta-analysis and systematic review. PLoS One. 2013;8:e73099.  https://doi.org/10.1371/journal.pone.0073099.Google Scholar
  43. 43.
    Lu Y, Ling G, Qiang C, Ming Q, Wu C, Wang K, et al. PCR Diagnosis of Pneumocystis pneumonia: a bivariate meta-analysis. J Clin Microbiol. 2011;49:4361–3.  https://doi.org/10.1128/JCM.06066-11.Google Scholar
  44. 44.
    White PL, Wingard JR, Bretagne S, Löffler J, Patterson TF, Slavin MA, et al. Aspergillus polymerase chain reaction: systematic review of evidence for clinical use in comparison with antigen testing. Clin Infect Dis. 2015;61(8):1293–303.  https://doi.org/10.1093/cid/civ507.Google Scholar
  45. 45.
    Vogel MN, Weissgerber P, Goeppert B, et al. Accuracy of serum LDH elevation for the diagnosis of Pneumocystis jiroveci pneumonia. Swiss Med Wkly. 2011;141:w13184.  https://doi.org/10.4414/smw.2011.13184.Google Scholar
  46. 46.
    Deng C, Li Y, Li Y. Systemic review: the accuracy of lactic dehydrogenase in the diagnosis of Pneumocystis pneumonia. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2018;30(4):322–6.  https://doi.org/10.3760/cma.j.issn.2095-4352.2018.04.007.Google Scholar
  47. 47.
    Nyamande K, Lalloo UG. Serum procalcitonin distinguishes CAP due to bacteria, Mycobacterium tuberculosis and PJP. Int J Tuberc Lung Dis. 2006;10:510–5.Google Scholar
  48. 48.
    Mendelson F, Griesel R, Tiffin N, Rangaka M, Boulle A, Mendelson M, et al. C-reactive protein and procalcitonin to discriminate between tuberculosis, Pneumocystis jirovecii pneumonia, and bacterial pneumonia in HIV-infected inpatients meeting WHO criteria for seriously ill: a prospective cohort study. BMC Infect Dis. 2018;18(1):399.  https://doi.org/10.1186/s12879-018-3303-6.Google Scholar
  49. 49.
    Schildgen V, Mai S, Khalfaoui S, et al. Pneumocystis jiroveci can be productively cultured in differentiated CuFi-8 airway cells. mBio. 2014;5(3):e01186–14.  https://doi.org/10.1128/mBio.01186-14.Google Scholar
  50. 50.
    Liu Y, Fahle GA, Kovacs JA. Inability to culture Pneumocystis jirovecii. MBio. 2018;9(3):e00939–18.  https://doi.org/10.1128/mBio.00939-18.Google Scholar
  51. 51.
    • Alanio A, Hauser PM, Lagrou K, Melchers WJ, Helweg-Larsen J, Matos O, et al. ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother. 2016;71(9):2386–96.  https://doi.org/10.1093/jac/dkw156 Provides a well thought diagnostic algorithm using both invasive and non-invasive samples that is applicable to all patient populations. Google Scholar
  52. 52.
    Cruciani M, Marcati P, Malena M, et al. Meta-analysis of diagnostic procedures for Pneumocystis carnii pneumonia in HIV-1-infected patients. Eur Respir J. 2002;20:982–9.Google Scholar
  53. 53.
    • Guegan H, Robert-Gangneux F. Molecular diagnosis of Pneumocystis pneumonia in immunocompromised patients. Curr Opin Infect Dis. 2019;32(4):314–21.  https://doi.org/10.1097/QCO.0000000000000559 Excellent overview of the molecular diagnosis of PcP, the likely future reference method for diagnosis. Google Scholar
  54. 54.
    Fraczek M, Ahmad S, Richardson M, Kirwan M, Bowyer P, Denning D, et al. Detection of Pneumocystis jirovecii by quantitative real-time PCR in oral rinses from Pneumocystis pneumonia asymptomatic human immunodeficiency virus patients. J Mycol Méd. 2019;29(2):107–11.  https://doi.org/10.1016/j.mycmed.2019.04.001.Google Scholar
  55. 55.
    Wang M, Dai X, Huang Y, Sun J, Dong X, Guo Y, et al. The presence of Pneumocystis jirovecii DNA in plasma is associated with a higher mortality rate in patients with AIDS-associated Pneumocystis pneumonia. Med Mycol. 2018.  https://doi.org/10.1093/mmy/myy110.
  56. 56.
    Choi J, Lee S, Leem A, Song J, Kim S, Chung K, et al. Pneumocystis jirovecii pneumonia (PCP) PCR-negative conversion predicts prognosis of HIV-negative patients with PCP and acute respiratory failure. PLoS One. 2018;13(10):e0206231.  https://doi.org/10.1371/journal.pone.0206231.Google Scholar
  57. 57.
    Roger PM, Vandenbos F, Pugliese P, De Salvador F, Durant J, Le Fichoux Y, et al. Persistence of Pneumocystis carinii after effective treatment of P. carinii pneumonia is not related to relapse or survival among patients infected with human immunodeficiency virus infection. Clin Infect Dis. 1998;26(2):509–10.  https://doi.org/10.1086/517099.Google Scholar
  58. 58.
    Matsumura Y, Tsuchido Y, Yamamoto M, Nakano S, Nagao M. Development of a fully automated PCR assay for the detection of Pneumocystis jirovecii using the GENECUBE system. Med Mycol. 2018.  https://doi.org/10.1093/mmy/myy145.
  59. 59.
    Sasso M, Chastang-Dumas E, Bastide S, Alonso S, Lechiche C, Bourgeois N, et al. Performances of four real-time PCR assays for the diagnosis of Pneumocystis jirovecii Pneumonia. J Clin Microbiol. 2016;54:625–30.  https://doi.org/10.1128/JCM.02876-15.Google Scholar
  60. 60.
    Lee CH, Helweg-Larsen J, Tang X, Jin S, Li B, Bartlett MS, et al. Update on Pneumocystis carinii f. sp. hominis typing based on nucleotide sequence variations in internal transcribed spacer regions of rRNA genes. J Clin Microbiol. 1998;36(3):734–41.Google Scholar
  61. 61.
    Lu JJ, Lee CH. Pneumocystis pneumonia. J Formos Med Assoc. 2008;107(11):830–42.  https://doi.org/10.1016/S0929-6646(08)60199-0.Google Scholar
  62. 62.
    Alanio A, Gits-Muselli M, Mercier-Delarue S, Dromer F, Bretagne S. Diversity of Pneumocystis jirovecii during Infection revealed by ultra-deep pyrosequencing. Front Microbiol. 2016;7:733.  https://doi.org/10.3389/fmicb.2016.00733.Google Scholar
  63. 63.
    Gits-Muselli M, Peraldi MN, de Castro N, Delcey V, Menotti J, Guigue N, et al. New short tandem repeat-based molecular typing method for Pneumocystis jirovecii reveals intrahospital transmission between patients from different wards. PLoS One. 2015;10(5):e0125763.  https://doi.org/10.1371/journal.pone.0125763.Google Scholar
  64. 64.
    Friedrich R, Rappold E, Bogdan C, Held J. Comparative analysis of the Wako β-Glucan test and the Fungitell assay for diagnosis of Candidemia and Pneumocystis jirovecii Pneumonia. J Clin Microbiol. 2018;56(9):e00464–18.  https://doi.org/10.1128/JCM.00464-18.Google Scholar
  65. 65.
    Mercier T, Guldentops E, Patteet S, Beuselinck K, Lagrou K, Maertens J. Beta-D-Glucan for diagnosing Pneumocystis pneumonia: a direct comparison between the Wako β-Glucan assay and the Fungitell assay. J Clin Microbiol. 2019;57(6):e00322–19.  https://doi.org/10.1128/JCM.00322-19.Google Scholar
  66. 66.
    White PL, Posso R, Gorton R, Price J, Wey E, Barnes R. An evaluation of the performance of the Dynamiker® Fungus (1–3)-β-D-Glucan assay to assist in the diagnosis of Pneumocystis pneumonia. Med Mycol. 2018;56(6):778–81.  https://doi.org/10.1093/mmy/myx097.Google Scholar
  67. 67.
    Karageorgopoulos D, Vouloumanou E, Ntziora F, Michalopoulos A, Rafailidis P, Falagas M. B-D-Glucan assay for the diagnosis of invasive fungal infections: a meta-analysis. Clin Infect Dis. 2011;52(6):750–70.  https://doi.org/10.1093/cid/ciq206.Google Scholar
  68. 68.
    Damiani C, Le Gal S, Da Costa C, Virmaux M, Nevez G, Totet A. Combined quantification of pulmonary Pneumocystis jirovecii DNA and serum (1-3)-β-D-glucan for differential diagnosis of pneumocystis pneumonia and Pneumocystis colonisation. J Clin Microbiol. 2013;51:3380–8.  https://doi.org/10.1128/JCM.01554-13.Google Scholar
  69. 69.
    de Boer MG, Gelinck LB, van Zelst BD, van de Sande WW, Willems LN, van Dissel JT, et al. β-D-glucan and S-adenosylmethionine serum levels for the diagnosis of Pneumocystis pneumonia in HIV-negative patients: a prospective study. J Inf Secur. 2011;62(1):93–100.  https://doi.org/10.1016/j.jinf.2010.10.007.Google Scholar
  70. 70.
    Rose SR, Vallabhajosyula S, Velez MG, Fedorko DP, VanRaden MJ, Gea-Banacloche JC, et al. The utility of bronchoalveolar lavage beta-D-glucan testing for the diagnosis of invasive fungal infections. J Inf Secur. 2014;69(3):278–83.  https://doi.org/10.1016/j.jinf.2014.04.008.Google Scholar
  71. 71.
    Salerno D, Mushatt D, Myers L, Zhuang Y, de la Rua N, Calderon EJ, et al. Serum and BAL beta-D-glucan for the diagnosis of Pneumocystis pneumonia in HIV positive patients. Respir Med. 2014;108:1688–95.  https://doi.org/10.1016/j.rmed.2014.09.017.Google Scholar
  72. 72.
    Rautemaa V, Green HD, Jones AM, Rautemaa-Richardson R. High level of β-(1,3)-d-glucan antigenaemia in cystic fibrosis in the absence of invasive fungal disease. Diagn Microbiol Infect Dis. 2017;88(4):316–21.  https://doi.org/10.1016/j.diagmicrobio.2017.05.010.Google Scholar
  73. 73.
    Fritzsche C, Ghanem H, Koball S, Mueller-Hilke B, Reisinger E. High Pneumocystis jirovecii colonization rate among haemodialysis patients. Infect Dis (Lond). 2017;49(2):132–6.  https://doi.org/10.1080/23744235.2016.1225980.Google Scholar
  74. 74.
    Esteves F, Lee CH, deSousa B, Badura R, Seringa M, Fernandes C, et al. (1-3)-beta-D-glucan in association with lactate dehydrogenase as biomarkers of Pneumocystis pneumonia (PcP) in HIV-infected patients. Eur J Clin Microbiol Infect Dis. 2014;33(7):1173–80.  https://doi.org/10.1007/s10096-014-2054-6.Google Scholar
  75. 75.
    Esteves f CSS, Badura R, de Boer MG, Maltez F, Calderón EJ, van der Reijden TJ, et al. Diagnosis of Pneumocystis pneumonia: evaluation of four serologic biomarkers. Clin Microbiol Infect. 2015;4(379):e1–10.  https://doi.org/10.1016/j.cmi.2014.11.025.Google Scholar
  76. 76.
    Maartens G, Stewart A, Griesel R, Kengne A, Dube F, Nicol M, et al. Development of a clinical prediction rule to diagnose Pneumocystis jirovecii pneumonia in the World Health Organization’s algorithm for seriously ill HIV-infected patients. S Afr J HIV Med. 2018;19(1):851.  https://doi.org/10.4102/sajhivmed.v19i1.851.Google Scholar
  77. 77.
    Azoulay E, Roux A, Vincent F, Kouatchet A, Argaud L, Rabbat A, et al. A Multivariable prediction model for Pneumocystis jirovecii Pneumonia in hematology patients with acute respiratory failure. Am J Respir Crit Care Med. 2018;198(12):1519–26.  https://doi.org/10.1164/rccm.201712-2452OC.Google Scholar
  78. 78.
    Green H, Paul M, Vidal L, et al. Prophylaxis of Pneumocystis pneumonia in immunocompromised non-HIV-infected patients: systematic review and meta-analysis of randomized controlled trials. Mayo Clin Proc. 2007;82:1052–9.  https://doi.org/10.4065/82.9.1052.Google Scholar
  79. 79.
    Alvarez B, Arcos J, Fernandez-Guerrero ML. Pulmonary infectious diseases in patients with primary immunodeficiency and those treated with biologic immunomodulating agents. Curr Opin Pulm Med. 2011;17:172–9.  https://doi.org/10.1097/MCP.0b013e3283455c0b.Google Scholar
  80. 80.
    Baddley JW, Winthrop KL, Chen L, Liu L, Grijalva CG, Delzell E, et al. Non-viral opportunistic infections in new users of tumour necrosis factor inhibitor therapy: results of the SAfety Assessment of Biologic ThERapy (SABER) Study. Ann Rheum Dis. 2014;73:1942–8.  https://doi.org/10.1136/annrheumdis-2013-203407.Google Scholar
  81. 81.
    Park JW, Curtis JR, Moon J, Song YW, Kim S, Lee EB. Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids. Ann Rheum Dis. 2018;77(5):644–9.  https://doi.org/10.1136/annrheumdis-2017-211796.Google Scholar
  82. 82.
    Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Accessed 11/09/2018, Page numbers B-1 to B-16.Google Scholar
  83. 83.
    Wang LI, Liang H, Ye LI, Jiang J, Liang B, Huang J. Adjunctive corticosteroids for the treatment of Pneumocystis jiroveci pneumonia in patients with HIV: a meta-analysis. Exp Ther Med. 2016;11(2):683–7.  https://doi.org/10.3892/etm.2015.2929.Google Scholar
  84. 84.
    Bollee G, Sarfati C, Thiery G, Bergeron A, de Miranda S, Menotti J, et al. Clinical picture of Pneumocystis jiroveci pneumonia in cancer patients. Chest. 2007;132:1305–10.  https://doi.org/10.1378/chest.07-0223.Google Scholar
  85. 85.
    Lemiale V, Debrumetz A, Delannoy A, Alberti C, Azoulay E. Adjunctive steroid in HIV-negative patients with severe Pneumocystis pneumonia. Respir Res. 2013;14:87.  https://doi.org/10.1186/1465-9921-14-87.Google Scholar
  86. 86.
    • Injean P, Eells SJ, Wu H, McElroy I, Gregson AL, McKinnell JA. A systematic review and meta-analysis of the data behind current recommendations for corticosteroids in non-HIV-related PCP: knowing when you are on shaky foundations. Transplant Direct. 2017;3(3):e137.  https://doi.org/10.1097/TXD.0000000000000642 Provides up-to-date information on the limitations and risks of using corticosteroids in the HIV-negative patient with PcP. Google Scholar
  87. 87.
    •• Yiannakis EP, Boswell TC. Systematic review of outbreaks of Pneumocystis jirovecii pneumonia: evidence that P. jirovecii is a transmissible organism and the implications for healthcare infection control. J Hosp Infect. 2016;93(1):1–8.  https://doi.org/10.1016/j.jhin.2016.01.018 Extensive review of PcP outbreaks, but also provides much needed infection control and outbreak advice. Google Scholar
  88. 88.
    Miller RF, Ambrose HE, Wakefield AE. Pneumocystis carinii f. sp. hominis DNA in immunocompetent health care workers in contact with patients with P. carinii pneumonia. J Clin Microbiol. 2001;39(11):3877–82.  https://doi.org/10.1128/JCM.39.11.3877-3882.2001.Google Scholar
  89. 89.
    Choukri F, Menotti J, Sarfati C, Lucet JC, Nevez G, Garin YJ, et al. Quantification and spread of Pneumocystis jirovecii in the surrounding air of patients with Pneumocystis pneumonia. Clin Infect Dis. 2010;51(3):259–65.  https://doi.org/10.1086/653933.Google Scholar
  90. 90.
    Yazaki H, Goto N, Uchida K, Kobayashi T, Gatanaga H, Oka S. Outbreak of Pneumocystis jiroveci pneumonia in renal transplant recipients: P. jiroveci is contagious to the susceptible host. Transplantation. 2009;88(3):380–5.  https://doi.org/10.1097/TP.0b013e3181aed389.Google Scholar
  91. 91.
    Argy N, Le Gal S, Coppée R, Song Z, Vindrios W, Massias L, et al. Pneumocystis Cytochrome b mutants associated with atovaquone prophylaxis failure as the cause of Pneumocystis infection outbreak among heart transplant recipients. Clin Infect Dis. 2018;67(6):913–9.  https://doi.org/10.1093/cid/ciy154.Google Scholar
  92. 92.
    Suárez I, Roderus L, van Gumpel E, Jung N, Lehmann C, Fätkenheuer G, et al. Low prevalence of DHFR and DHPS mutations in Pneumocystis jirovecii strains obtained from a German cohort. Infection. 2017;45(3):341–7.  https://doi.org/10.1007/s15010-017-1005-4.Google Scholar
  93. 93.
    Ponce CA, Chabé M, George C, Cárdenas A, Durán L, Guerrero J, et al. High prevalence of Pneumocystis jirovecii dihydropteroate synthase gene mutations in patients with a first episode of Pneumocystis pneumonia in Santiago, Chile, and clinical response to trimethoprim-sulfamethoxazole therapy. Antimicrob Agents Chemother. 2017;61(2):e01290–16.  https://doi.org/10.1128/AAC.01290-16.Google Scholar
  94. 94.
    Hauser PM, Nahimana A, Taffe P, Weber R, Francioli P, Bille J, et al. Interhuman transmission as a potential key parameter for geographical variation in the prevalence of Pneumocystis jirovecii dihydropteroate synthase mutations. Clin Infect Dis. 2010;51(4):e28–33.  https://doi.org/10.1086/655145.Google Scholar
  95. 95.
    Huang L, Beard CB, Creasman J, Levy D, Duchin JS, Lee S, et al. Sulfa or sulfone prophylaxis and geographic region predict mutations in the Pneumocystis carinii dihydropteroate synthase gene. J Infect Dis. 2000;182(4):1192–8.  https://doi.org/10.1086/315824.Google Scholar
  96. 96.
    Panel on Opportunistic Infections in HIV-exposed and HIV-Infected children. Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-Infected children. Department of Health and Human Services. Accessed 11/10/2016, Page numbers W-1 to W-16.Google Scholar
  97. 97.
    Basiaga ML, Ross ME, Gerber JS, Ogdie A. Incidence of Pneumocystis jirovecii and adverse events associated With Pneumocystis prophylaxis in children receiving glucocorticoids. J Pediatr Infect Dis Soc. 2018, 7(4):283–9.  https://doi.org/10.1093/jpids/pix052.
  98. 98.
    • Katragkou A, Fisher BT, Groll AH, Roilides E, Walsh TJ. Diagnostic imaging and invasive fungal diseases in children. J Pediatr Infect Dis Soc. 2017;1(6):S22–31.  https://doi.org/10.1093/jpids/pix055 Good overview of typical paediatric radiology associated with invasive fungal disease. Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • P. Lewis White
    • 1
    Email author
  • Jessica S. Price
    • 1
  • Matthijs Backx
    • 1
  1. 1.Public Health Wales Microbiology Cardiff, UHW, Heath ParkCardiffUK

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