Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Clinical presentation and diagnosis of Pneumocystis pulmonary infection in HIV-infected patients

Paul E Sax, MD
Section Editor
John G Bartlett, MD
Deputy Editor
Jennifer Mitty, MD, MPH


The incidence of Pneumocystis jirovecii (previously named Pneumocystis carinii) pneumonia has dramatically declined due to effective antiretroviral therapy (ART) and, to a lesser extent, the use of prophylaxis. Despite this decrease, it remains one of the leading causes of opportunistic infections among HIV-infected persons with low CD4 cell counts, such as those who are unaware of their HIV diagnoses or are not receiving medical care.

The general features of Pneumocystis pulmonary infection in the HIV-infected patient, including clinical presentation and diagnosis, will be reviewed here. An overview of extrapulmonary disease due to pneumocystic infection will also be discussed. Treatment and prophylaxis of Pneumocystis infection in HIV-infected and non-infected individuals are considered elsewhere. (See "Treatment and prevention of Pneumocystis infection in HIV-infected patients" and "Treatment and prevention of Pneumocystis pneumonia in HIV-uninfected patients".)


Pneumocystis is currently recognized as a fungus based upon ribosomal RNA and other gene sequence homologies, the composition of their cell walls, and the structure of key enzymes [1]. Prior to being identified as a fungus, the taxonomic classification of Pneumocystis as a genus of protozoan organisms had been questioned for several years. However, Pneumocystis organisms are atypical fungi as they do not grow in fungal culture, they respond to some antiparasitic agents, and they have a cell wall that contains cholesterol rather than ergosterol [2]. The life cycle consists of the trophic form, a precystic form, and the cystic form [3]. The trophic form predominates over the cystic form during infection.

The nomenclature for Pneumocystis has also changed; four species have now been described: two that infect rats, including P. carinii; and one that infects humans, P. jirovecii [4]. P. jirovecii is now designated as the species name to use in publications and references to human infections [4,5]. However, the abbreviation of "PCP" is still used to refer to the clinical entity of "Pneumocystis Pneumonia"; this allows for the retention of the familiar acronym and maintains the accuracy of this abbreviation in older published papers.


Transmission — The primary mode of transmission of P. jirovecii is via the airborne route. Serologic studies show that primary infection occurs early in life, with 75 percent of humans infected by the age of four years [6]. It was initially believed that PCP remained in a latent state unless the patient became immunosuppressed; however, this may not account for all cases of PCP. Animal and human studies have shown clearance of the organism, and there is increasing evidence of transmission from person to person and possibly through environmental reservoirs [7-11]. The role of colonization in humans may also be of importance to Pneumocystis transmission. (See 'Colonization' below.)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Oct 3, 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Edman JC, Kovacs JA, Masur H, et al. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the fungi. Nature 1988; 334:519.
  2. Catherinot E, Lanternier F, Bougnoux ME, et al. Pneumocystis jirovecii Pneumonia. Infect Dis Clin North Am 2010; 24:107.
  3. Huang L, Morris A, Limper AH, et al. An Official ATS Workshop Summary: Recent advances and future directions in pneumocystis pneumonia (PCP). Proc Am Thorac Soc 2006; 3:655.
  4. Cushion MT, Stringer JR. Has the name really been changed? It has for most researchers. Clin Infect Dis 2005; 41:1756.
  5. Gigliotti F. Pneumocystis carinii: has the name really been changed? Clin Infect Dis 2005; 41:1752.
  6. Pifer LL, Hughes WT, Stagno S, Woods D. Pneumocystis carinii infection: evidence for high prevalence in normal and immunosuppressed children. Pediatrics 1978; 61:35.
  7. Dohn MN, White ML, Vigdorth EM, et al. Geographic clustering of Pneumocystis carinii pneumonia in patients with HIV infection. Am J Respir Crit Care Med 2000; 162:1617.
  8. Morris AM, Swanson M, Ha H, Huang L. Geographic distribution of human immunodeficiency virus-associated Pneumocystis carinii pneumonia in San Francisco. Am J Respir Crit Care Med 2000; 162:1622.
  9. Choukri F, Menotti J, Sarfati C, et al. Quantification and spread of Pneumocystis jirovecii in the surrounding air of patients with Pneumocystis pneumonia. Clin Infect Dis 2010; 51:259.
  10. Huang L, Cattamanchi A, Davis JL, et al. HIV-associated Pneumocystis pneumonia. Proc Am Thorac Soc 2011; 8:294.
  11. Krajicek BJ, Limper AH, Thomas CF Jr. Advances in the biology, pathogenesis and identification of Pneumocystis pneumonia. Curr Opin Pulm Med 2008; 14:228.
  12. Stringer JR, Keely SP. Genetics of surface antigen expression in Pneumocystis carinii. Infect Immun 2001; 69:627.
  13. Davis JL, Welsh DA, Beard CB, et al. Pneumocystis colonisation is common among hospitalised HIV infected patients with non-Pneumocystis pneumonia. Thorax 2008; 63:329.
  14. Morris A, Wei K, Afshar K, Huang L. Epidemiology and clinical significance of pneumocystis colonization. J Infect Dis 2008; 197:10.
  15. Hoover DR, Saah AJ, Bacellar H, et al. Clinical manifestations of AIDS in the era of pneumocystis prophylaxis. Multicenter AIDS Cohort Study. N Engl J Med 1993; 329:1922.
  16. Wolff AJ, O'Donnell AE. Pulmonary manifestations of HIV infection in the era of highly active antiretroviral therapy. Chest 2001; 120:1888.
  17. San-Andrés FJ, Rubio R, Castilla J, et al. Incidence of acquired immunodeficiency syndrome-associated opportunistic diseases and the effect of treatment on a cohort of 1115 patients infected with human immunodeficiency virus, 1989-1997. Clin Infect Dis 2003; 36:1177.
  18. Buchacz K, Baker RK, Palella FJ Jr, et al. AIDS-defining opportunistic illnesses in US patients, 1994-2007: a cohort study. AIDS 2010; 24:1549.
  19. Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE), Mocroft A, Reiss P, et al. Is it safe to discontinue primary Pneumocystis jiroveci pneumonia prophylaxis in patients with virologically suppressed HIV infection and a CD4 cell count <200 cells/microL? Clin Infect Dis 2010; 51:611.
  20. Worodria W, Davis JL, Cattamanchi A, et al. Bronchoscopy is useful for diagnosing smear-negative tuberculosis in HIV-infected patients. Eur Respir J 2010; 36:446.
  21. Worodria W, Okot-Nwang M, Yoo SD, Aisu T. Causes of lower respiratory infection in HIV-infected Ugandan adults who are sputum AFB smear-negative. Int J Tuberc Lung Dis 2003; 7:117.
  22. Lundberg BE, Davidson AJ, Burman WJ. Epidemiology of Pneumocystis carinii pneumonia in an era of effective prophylaxis: the relative contribution of non-adherence and drug failure. AIDS 2000; 14:2559.
  23. Fei MW, Sant CA, Kim EJ, et al. Severity and outcomes of Pneumocystis pneumonia in patients newly diagnosed with HIV infection: an observational cohort study. Scand J Infect Dis 2009; 41:672.
  24. 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 http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. (Accessed on July 08, 2014).
  25. Kales CP, Murren JR, Torres RA, Crocco JA. Early predictors of in-hospital mortality for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Arch Intern Med 1987; 147:1413.
  26. Stansell JD, Osmond DH, Charlebois E, et al. Predictors of Pneumocystis carinii pneumonia in HIV-infected persons. Pulmonary Complications of HIV Infection Study Group. Am J Respir Crit Care Med 1997; 155:60.
  27. Bozzette SA, Finkelstein DM, Spector SA, et al. A randomized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group. N Engl J Med 1995; 332:693.
  28. Phair J, Muñoz A, Detels R, et al. The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1. Multicenter AIDS Cohort Study Group. N Engl J Med 1990; 322:161.
  29. Miller RF, Huang L, Walzer PD. Pneumocystis pneumonia associated with human immunodeficiency virus. Clin Chest Med 2013; 34:229.
  30. Stover DE, Meduri GU. Pulmonary function tests. Clin Chest Med 1988; 9:473.
  31. Stover DE, Greeno RA, Gagliardi AJ. The use of a simple exercise test for the diagnosis of Pneumocystis carinii pneumonia in patients with AIDS. Am Rev Respir Dis 1989; 139:1343.
  32. Smith DE, Forbes A, Davies S, et al. Diagnosis of Pneumocystis carinii pneumonia in HIV antibody positive patients by simple outpatient assessments. Thorax 1992; 47:1005.
  33. Zaman MK, White DA. Serum lactate dehydrogenase levels and Pneumocystis carinii pneumonia. Diagnostic and prognostic significance. Am Rev Respir Dis 1988; 137:796.
  34. Butt AA, Michaels S, Kissinger P. The association of serum lactate dehydrogenase level with selected opportunistic infections and HIV progression. Int J Infect Dis 2002; 6:178.
  35. Sax PE, Komarow L, Finkelman MA, et al. Blood (1->3)-beta-D-glucan as a diagnostic test for HIV-related Pneumocystis jirovecii pneumonia. Clin Infect Dis 2011; 53:197.
  36. Huang L, Stansell J, Osmond D, et al. Performance of an algorithm to detect Pneumocystis carinii pneumonia in symptomatic HIV-infected persons. Pulmonary Complications of HIV Infection Study Group. Chest 1999; 115:1025.
  37. DeLorenzo LJ, Huang CT, Maguire GP, Stone DJ. Roentgenographic patterns of Pneumocystis carinii pneumonia in 104 patients with AIDS. Chest 1987; 91:323.
  38. Jules-Elysee KM, Stover DE, Zaman MB, et al. Aerosolized pentamidine: effect on diagnosis and presentation of Pneumocystis carinii pneumonia. Ann Intern Med 1990; 112:750.
  39. Sepkowitz KA, Telzak EE, Gold JW, et al. Pneumothorax in AIDS. Ann Intern Med 1991; 114:455.
  40. Metersky ML, Colt HG, Olson LK, Shanks TG. AIDS-related spontaneous pneumothorax. Risk factors and treatment. Chest 1995; 108:946.
  41. Gruden JF, Huang L, Turner J, et al. High-resolution CT in the evaluation of clinically suspected Pneumocystis carinii pneumonia in AIDS patients with normal, equivocal, or nonspecific radiographic findings. AJR Am J Roentgenol 1997; 169:967.
  42. Hartman TE, Primack SL, Müller NL, Staples CA. Diagnosis of thoracic complications in AIDS: accuracy of CT. AJR Am J Roentgenol 1994; 162:547.
  43. Hidalgo A, Falcó V, Mauleón S, et al. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol 2003; 13:1179.
  44. Tuazon CU, Delaney MD, Simon GL, et al. Utility of gallium67 scintigraphy and bronchial washings in the diagnosis and treatment of Pneumocystis carinii pneumonia in patients with the acquired immune deficiency syndrome. Am Rev Respir Dis 1985; 132:1087.
  45. Fisk DT, Meshnick S, Kazanjian PH. Pneumocystis carinii pneumonia in patients in the developing world who have acquired immunodeficiency syndrome. Clin Infect Dis 2003; 36:70.
  46. O'Donnell WJ, Pieciak W, Chertow GM, et al. Clearance of Pneumocystis carinii cysts in acute P carinii pneumonia: assessment by serial sputum induction. Chest 1998; 114:1264.
  47. Roger PM, Vandenbos F, Pugliese P, 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. Clin Infect Dis 1998; 26:509.
  48. Levine SJ, Masur H, Gill VJ, et al. Effect of aerosolized pentamidine prophylaxis on the diagnosis of Pneumocystis carinii pneumonia by induced sputum examination in patients infected with the human immunodeficiency virus. Am Rev Respir Dis 1991; 144:760.
  49. Zaman MK, Wooten OJ, Suprahmanya B, et al. Rapid noninvasive diagnosis of Pneumocystis carinii from induced liquefied sputum. Ann Intern Med 1988; 109:7.
  50. Cruciani M, Marcati P, Malena M, et al. Meta-analysis of diagnostic procedures for Pneumocystis carinii pneumonia in HIV-1-infected patients. Eur Respir J 2002; 20:982.
  51. Willocks L, Burns S, Cossar R, Brettle R. Diagnosis of Pneumocystis carinii pneumonia in a population of HIV-positive drug users, with particular reference to sputum induction and fluorescent antibody techniques. J Infect 1993; 26:257.
  52. Levine SJ, Kennedy D, Shelhamer JH, et al. Diagnosis of Pneumocystis carinii pneumonia by multiple lobe, site-directed bronchoalveolar lavage with immunofluorescent monoclonal antibody staining in human immunodeficiency virus-infected patients receiving aerosolized pentamidine chemoprophylaxis. Am Rev Respir Dis 1992; 146:838.
  53. Benfield TL, Prentø P, Junge J, et al. Alveolar damage in AIDS-related Pneumocystis carinii pneumonia. Chest 1997; 111:1193.
  54. Alvarez F, Bandi V, Stager C, Guntupalli KK. Detection of Pneumocystis carinii in tracheal aspirates of intubated patients using calcofluor-white (Fungi-Fluor) and immunofluorescence antibody (Genetic Systems) stains. Crit Care Med 1997; 25:948.
  55. Wood BR, Komarow L, Zolopa AR, et al. Test performance of blood beta-glucan for Pneumocystis jirovecii pneumonia in patients with AIDS and respiratory symptoms. AIDS 2013; 27:967.
  56. Kovacs JA, Gill VJ, Meshnick S, Masur H. New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia. JAMA 2001; 286:2450.
  57. Fischer S, Gill VJ, Kovacs J, et al. The use of oral washes to diagnose Pneumocystis carinii pneumonia: a blinded prospective study using a polymerase chain reaction-based detection system. J Infect Dis 2001; 184:1485.
  58. Oz HS, Hughes WT. Search for Pneumocystis carinii DNA in upper and lower respiratory tract of humans. Diagn Microbiol Infect Dis 2000; 37:161.
  59. Greenberg SD, Frager D, Suster B, et al. Active pulmonary tuberculosis in patients with AIDS: spectrum of radiographic findings (including a normal appearance). Radiology 1994; 193:115.
  60. Barnes PF, Bloch AB, Davidson PT, Snider DE Jr. Tuberculosis in patients with human immunodeficiency virus infection. N Engl J Med 1991; 324:1644.
  61. Rabaud C, May T, Lucet JC, et al. Pulmonary toxoplasmosis in patients infected with human immunodeficiency virus: a French National Survey. Clin Infect Dis 1996; 23:1249.
  62. Pomeroy C, Filice GA. Pulmonary toxoplasmosis: a review. Clin Infect Dis 1992; 14:863.
  63. Ng VL, Yajko DM, Hadley WK. Extrapulmonary pneumocystosis. Clin Microbiol Rev 1997; 10:401.