Skip to main content

Advertisement

SpringerLink
Log in

Diagnosis, Burden and Mortality of Pneumocystis jirovecii Pneumonia in Venezuela

  • Clinical Mycology Lab Issues (S Cordoba, Section Editor)
  • Published:
Current Fungal Infection Reports Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

  1. •• Calderón-Sandubete EJ, Varela-Aguilar JM, Medrano-Ortega FJ, Nieto-Guerrero V, Respaldiza-Salas N, de la Horra-Padilla C, et al. Historical perspective on Pneumocystis carinii infection. Protist. 2002;153(3):303–10. https://doi.org/10.1078/1434-4610-00107This paper highlights the need to continue studyingP. jiroveciiin order to improve knowledge of its epidemiology in general population.

    Article  PubMed  Google Scholar 

  2. Miller R, Huang L. Pneumocystis jirovecii infection. Thorax. 2004;59:731–3. https://doi.org/10.1136/thx.2004.021436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Thomas CF Jr, Limper AH. Pneumocystis pneumonia. N Engl J Med. 2004;350:2487–98. https://doi.org/10.1056/NEJMra032588.

    Article  CAS  PubMed  Google Scholar 

  4. •• Calderón EJ, Gutiérrez-Rivero S, Durand-Joly I, Dei-Cas E. Pneumocystis infection in humans: diagnosis and treatment. Expert Rev Anti-Infect Ther. 2010;8(6):683–701. https://doi.org/10.1586/eri.10.42This review exposes information about clinical manifestations, laboratory diagnosis, treatment, and prophylaxis of PCP, in addition to an expert commentary and a five-year view.

    Article  PubMed  Google Scholar 

  5. • Panizo MM, Reviakina V, Navas T, Casanova K, Sáez A, Guevara RN, et al. Neumocistosis en pacientes venezolanos: diagnóstico y epidemiología (2001–2006). Rev Iberoam Micol. 2008;25:226–231. Available in: http://reviberoammicol.com/2008-25/226231.pdf. Accessed 5 November, 2019. This is the first report of PCP incidence through passive surveillance in Venezuela, published by the national reference center, the RRNIH.

  6. Decker CF, Masur H. Pneumocystosis. In: Kauffman CA, Pappas PG, Sobel JD, Dismukes WE, editors. Essentials of clinical mycology. Second Edition. New York, USA: Springer Science Business Media, LLC; 2011. pp 437–453. https://doi.org/10.1007/978-1-4419-6640-7_26.

    Google Scholar 

  7. •• Medrano FJ, Montes-Cano M, Conde M, de la Horra C, Respaldiza N, Gasch A, et al. Pneumocystis jirovecii in general population. Emerg Infect Dis. 2005;11:245–250. https://doi.org/10.3201/eid1102.040487. This study provides the first evidence thatP. jiroveciiDNA 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.

    Article  PubMed  PubMed Central  Google Scholar 

  8. White PL, Price JS, Backx M. Pneumocystis jirovecii pneumonia: epidemiology, clinical manifestation and diagnosis. Curr Fung Infect Rep. 2019;13:260–73. https://doi.org/10.1007/s12281-019-00349-3.

    Article  Google Scholar 

  9. Cruciani M, Marcati P, Malena M, Bosco O, Serpelloni G, Mengoli C. Meta-analysis of diagnostic procedures for Pneumocystis carinii pneumonia in HIV-infected patients. Eur Respir J. 2002;20:982–9. https://doi.org/10.1183/09031936.02.01372002.

    Article  CAS  PubMed  Google Scholar 

  10. •• Tomás AL, Matos O. Pneumocystis jirovecii pneumonia: current advances in laboratory diagnosis. OBM Genetics. 2018;2(4). https://doi.org/10.21926/obm.genet.1804049This review presents the last advances in laboratory diagnosis of PCP, and exposes the need to have faster and inexpensive screening and diagnosis tests for this disease, in order to improve therapeutic interventions, disease control, and provide retrenchment to healthcare systems.

    Article  Google Scholar 

  11. • Casanova K, Sáez A, Navas T, Reviakina V, Panizo M, Chiriboga D. Epidemiología de la neumocistosis Med Interna (Caracas). 2006;22(3):207–226. Available in: http://svmi.web.ve/wh/revista/V22_N3.pdf. Accesed 17 October, 2019. In this paper the authors concluded that PCP should be suspected in patients without AIDS and risk factors for the disease, recommending DIF as the choice technique for diagnosis. The great contribution of this study was to calculate the diagnostic capacity of signs, symptoms, radiological findings, and arterial gases among others, based on DIF’s results.

  12. • Moreno Calderón X, Reviákina V, Panizo MM, León M. Diagnóstico de neumocistosis en pacientes oncológicos por la técnica de inmunofluorescencia directa Rev Venez Oncol. 2010;22(4):222–231. Available in: https://www.redalyc.org/pdf/3756/375634865002.pdf. Accesed 5 July, 2019. This study focused on knowing PCP frequency in cancer patients, using DIF with IS, LBA and tracheal aspirates specimens, getting excellent results with serial specimens of IS and recommending its use.

  13. • Panizo MM, Ferrara G, García N, Reviakina V, Navas T, Moreno X, Capote AM, Dolande M, Alarcón V, Calderón E. Pneumocystis jirovecii in HIV patients and suspected pneumonia: a problematic diagnosis in Caracas, Venezuela. Invest Clin. 2019. (In Press). This is the second incidence report of PCP through passive surveillance only in HIV patients with suspected pneumonia, published by the national reference center, the RRNIH.

  14. • Panizo MM, Ferrara G, García N, Moreno X, Navas T, Calderón E, on behalf of the Venezuelan Group for the Study of Pneumocystosis belonging to the Iberoamerican Pneumocystosis Network (IBEROPNEUMOCYSTIS). Epidemiology of Pneumocystis jirovecii pneumonia in Venezuela. Curr Fung Infect Rep. 2020; (In Press). This paper contributes to the knowledge of PCP epidemiology in Venezuela, by an updated review of the information currently available.

  15. • Panizo MM, Dolande M, Ferrara G, Alarcón V, García N, Reviakina V, Capote AM, Navas T, Moreno X, Alastruey-Izquierdo A, Denning DW. The burden of serious fungal infections in Venezuela. 7th Trends in Medical Mycology. Conference Abstracts. Abstract P212. Available in: https://www.gaffi.org/wp-content/uploads/BurdenFungalInfectionsVenezuela_P212_Final.ppt. Accesed 5 November, 2019. This is the first risk estimation of fungal diseases acquisition in Venezuelan population, carried out by the national reference center, the RRNIH.

  16. Global Action Fund for Fungal Infections. Improving outcomes for patients with fungal infections across the world. A road map for the next decade. 95/95 by 2025. Available in: https://www.gaffi.org/wp-content/uploads/GAFFI_Road_Map_interactive-final0415.pdf. Accesed 15 September, 2019.

  17. Global Action Fund for Fungal Infections. GAFFI Fact Sheet. Pneumocystis pneumonia. Available in: https://www.gaffi.org/wp-content/uploads/Briefing-note-PCP-GAFFI-December-2017-V4.pdf. Accesed 15 September, 2019.

  18. Organización Panamericana de la Salud. Clasificación estadística internacional de enfermedades y problemas relacionados con la salud. 10a. revisión. Washington, D.C.: OPS; 1995. Available in: http://ais.paho.org/classifications/Chapters/pdf/Volume2.pdf. Accesed 15 October, 2019.

  19. Chackiel, J. La investigación sobre causas de muerte en América Latina. Situación actual y perspectivas futuras. CELADE. 1986. Pp. 1–27. Available in: https://repositorio.cepal.org/bitstream/handle/11362/20854/D-12026.01_es.pdf?sequence=1&isAllowed=y. Accesed 7 October, 2019.

  20. García Pérez DM, Muñoz C. Calidad de la certificación de la causa básica de la muerte. Estado Lara 1995. Boletín Médico de Postgrado. 2001;VIII(2). Available in: http://bibvirtual.ucla.edu.ve/db/psm_ucla/edocs/bm/BM1702/BM170204.pdf. Accesed 15 October, 2019.

  21. Suárez de Díaz CE, Suárez D. Calidad en el certificado de defunción. Hospital “Ruiz y Páez”, 2005. SABER. Revista Multidisciplinaria del Consejo de Investigación de la Universidad de Oriente. 2007;19(1):56–64. Available in: https://www.redalyc.org/pdf/4277/427739431010.pdf. Accesed 15 October, 2019.

  22. • Borelli K, Brito A, Rivas G, Panizo MM, Roldán Y. Diagnóstico de Pneumocystis carinii: Estudio comparativo entre la inmunofluorescencia directa y la coloración histológica de Gomori-Grocott Rev Soc Venez Microbiol 2000;20(1):46–52. Available in: http://ve.scielo.org/scielo.php?script=sci_arttext&pid=S1315-25562000000100010&lng=es&nrm=iso&tlng=es. Accesed 5 July, 2019. This is the first comparative study between DIF and Gomori-Grocott stain for PCP diagnosis, carried out at the national reference center, the RRNIH.

  23. • Panizo MM, Alarcón V, Reviakina V, Navas T. Evaluación de la técnica de PCR anidada para el diagnóstico de Pneumocystis jirovecii. Rev Soc Venez Microbiol 2009;29:136–139. Available in: http://ve.scielo.org/pdf/rsvm/v29n2/art13.pdf. Accesed 7 July, 2019. This study corresponds to the introduction of nPCR forP. jiroveciidetection by the RRNIH, through a comparative study between DIF (chosen as the gold standard test) and nPCR.

  24. Bava AJ, Cattaneo S, Bellegarde E. Diagnosis of pulmonary pneumocystosis by microscopy on wet mount preparations. Rev Inst Med Trop S Paulo. 2002;44:279–82. https://doi.org/10.1590/S0036-46652002000500009.

    Article  PubMed  Google Scholar 

  25. Baughman RP, Strohoper SS, Clinton BA, Nickol AD, Frame PI. The use of an indirect fluorescent antibody test for detecting Pneumocystis carinii. Arch Pathol Lab Med. 1989;113:1062–5.

    CAS  PubMed  Google Scholar 

  26. Lautenschlager I, Lyytikainen O, Jokipii L, Jokipii A, Maiche A, Ruutu T, et al. Immunodetection of Pneumocystis carinii in bronchoalveolar lavage specimens compared with methenamine silver stain. J Clin Microbiol. 1996;34:728–730. Available in: https://jcm.asm.org/content/jcm/34/3/728.full.pdf. Accesed 15 June, 2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Procop GW, Haddad S, Quinn J, Wilson ML, Henshaw NG, Reller LB, et al. Detection of Pneumocystis jiroveci in respiratory specimens by four staining methods. J Clin Microbiol. 2004;42:3333–5. https://doi.org/10.1128/JCM.42.7.3333-3335.2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Aderaye G, Woldeamanuel Y, Asrat D, Lebbad M, Beser J, Worku A, et al. Evaluation of toluidine blue O staining for the diagnosis of Pneumocystis jiroveci in expectorated sputum sample and bronchoalveolar lavage from HIV-infected patients in a tertiary care referral center in Ethiopia. Infection. 2008;36:237–43. https://doi.org/10.1007/s15010-007-7191-8.

    Article  CAS  PubMed  Google Scholar 

  29. Raab SS, Cheville JC, Bottles K, Cohen MB. Utility of Gomori methenamine silver stains in bronchoalveolar lavage specimens. Mod Pathol. 1994;7:599–604.

    CAS  PubMed  Google Scholar 

  30. Galan F, Oliver JL, Roux P, Poirot JL, Bereziat G. Detection of Pneumocystis carinii DNA by polymerase chain reaction compared to direct microscopy and immunofluorescence. J Protozool. 1991;38:199S–200S.

    CAS  PubMed  Google Scholar 

  31. Fan LC, Lu HW, Cheng KB, Li HP, Xu JF. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Summah H, Zhu YG, Falagas ME, Vouloumanou EK, Qu JM. 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. https://doi.org/10.3760/cma.j.issn.0366-6999.20122506.

    Article  PubMed  Google Scholar 

  33. •• Calderón EJ, de Armas Y, Panizo MM, Wissmann G. Pneumocystis jirovecii pneumonia in Latin America. A public health problem? Expert Rev Anti-Infect Ther. 2013;11:565–70. https://doi.org/10.1586/eri.13.41This 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 HAART coverage, as well as in the observed frequencies of PCP that range from 5.9 to 55% in this area.

    Article  CAS  PubMed  Google Scholar 

  34. •• De Armas Rodríguez Y, Wissmann G, Müller AL, Pederiva MA, Brum MC, Brackmann RL, et al. Pneumocystis jirovecii pneumonia in developing countries. Parasite. 2011;18:219–28. https://doi.org/10.1051/parasite/2011183219 Accesed 5 July, 2019. This article revealed that in most developing countries, relatively little is known about the prevalence of PCP, and this disease was identified as a frequent opportunistic infection in AIDS patients from different geographic regions.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ebner L, Walti LN, Rauch A, Furrer H, Cusini A, Meyer AMJ, et al. Clinical course, radiological manifestations, and outcome of Pneumocystis jirovecii pneumonia in HIV patients and renal transplant recipients. PLoS One. 2016;11:e0164320. https://doi.org/10.1371/journal.pone.0164320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Rodriguez M, Fishman JA. Prevention of infection due to Pneumocystis spp. in human immunodeficiency virus-negative immunocompromised patients. Clin Microbiol Rev. 2004;17:770–82. https://doi.org/10.1128/CMR.17.4.770-782.2004.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Rossiter SJ, Miller DC, Churg AM, et al. Open lung biopsy in the immunosuppressed patient. Is it really beneficial? J Thorac Cardiovasc Surg. 1979;77:338–45.

    Article  CAS  PubMed  Google Scholar 

  38. Du Plessis D, Poonsamy B, Msimang V, Davidsson L, Cohen C, Govender N, et al. Laboratory-based surveillance of Pneumocystis jirovecii pneumonia in South Africa, 2006-2010. South Afr J Infect Dis. 2016;31:8–13. https://doi.org/10.1080/23120053.2015.1118828.

    Article  Google Scholar 

  39. Rabodonirina M, Raffenot D, Cotte L, Boibieux A, Mayençon M, Bayle G, et al. Rapid detection of Pneumocystis carinii in bronchoalveolar lavage specimens from human immunodeficiency virus-infected patients: use of a simple DNA extraction procedure and nested PCR J Clin Microbiol. 1997;35:2748–2751. Available in: https://jcm.asm.org/content/jcm/35/11/2748.full.pdf. Accesed 15 June, 2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wakefield AE, Guiver L, Miller RF, Hopkin JM. DNA amplification on induced sputum samples for diagnosis of Pneumocystis carinii pneumonia. Lancet. 1991;337:1378–9. https://doi.org/10.1016/0140-6736(91)93062-E.

    Article  CAS  PubMed  Google Scholar 

  41. LaRocque RC, Katz JT, Perruzzi P, Baden LR. The utility of sputum induction for diagnosis of Pneumocystis pneumonia in immunocompromised patients without human immunodeficiency virus. Clin Infect Dis. 2003;37:1380–3. https://doi.org/10.1086/379071.

    Article  PubMed  Google Scholar 

  42. Fishman JA. Pneumocystis carinii and parasitic infection in the immunocompromised host. In: Clinical approach to infection in the compromised host. New York: Kluwer Academic/Plenum Publishers; 2002. p. 265–334.

    Chapter  Google Scholar 

  43. Choe PG, Kang YM, Kim G, Park WB, Park SW, Kim HB, et al. Diagnostic value of direct fluorescence antibody staining for detecting Pneumocystis jirovecii in expectorated sputum from patients with HIV infection. Med Mycol. 2014;52:326–30. https://doi.org/10.1093/mmy/myu002.

    Article  CAS  PubMed  Google Scholar 

  44. Siegel M, Masur H, Kovacs J. Pneumocystis jirovecii pneumonia in human immunodeficiency infection. Semin Respir Crit Care Med. 2016;37:243–56. https://doi.org/10.1055/s-0036-1579556.

    Article  PubMed  Google Scholar 

  45. Pinlaor S, Mootsikapum P, Pinlaor P, Phunmanee A, Pipitgool V, Sithithaworn P, et al. PCR diagnosis of Pneumocystis carinii sputum and bronchoalveolar lavage samples in immuno-compromised patients. Parasitol Res. 2004;94:213–8. https://doi.org/10.1007/s00436-004-1200-y.

    Article  PubMed  Google Scholar 

  46. Kovacs JA, Ng VL, Masur H, Leoung G, Hadley WK, Evans G, et al. Diagnosis of Pneumocystis carinii pneumonia: improved detection in sputum with use of monoclonal antibodies. New Engl J Med. 1988;318:589–93. https://doi.org/10.1056/NEJM198803103181001.

    Article  CAS  PubMed  Google Scholar 

  47. Ng VL, Virani NA, Chaisson RE, et al. Rapid detection of Pneumocystis carinii using a direct fluorescent monoclonal antibody stain. J Clin Microbiol. 1990;28:2228–33 Available in: https://jcm.asm.org/content/jcm/28/10/2228.full.pdf. Accesed 5 June, 2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. • Chimá Rodríguez L, Navas Blasnco TM, Panizo MM. Diagnóstico de neumocistosis a través de la inmunofluorescencia directa y la PCR anidada en pacientes con enfermedad pulmonar obstructiva crónica. Med Inter (Caracas). 2013;29(4):223–31 Available in: http://www.svmi.web.ve/ojs/index.php/medint/article/view/86. Accesed 7 September, 2019. In this study PCP was demonstrated by DIF and nPCR in patients with COPD exacerbation, and colonization was demonstrated through nPCR in patients with COPD without exacerbation.

    Google Scholar 

  49. • Carrillo E, Marelli A, Reviakina V, Panizo M, Navas T. Positividad de la inmunofluorescencia directa para Pneumocystis jirovecii en contactos de pacientes con neumocistosis. Med Inter (Caracas). 2008;24:216–30 Available in: http://www.svmi.web.ve/wh/revista/V24_N4.pdf#page=40. Accesed 7 September, 2019. In this study DIF was effective in the diagnosis of PCP in AIDS patientes, and inP. jiroveciidetection in asymptomatic immunocompetent people in contact with AIDS patients.

    Google Scholar 

  50. • Panizo MM, Reviakina V, Navas T, García N, Alarcón V, Marelli A, et al. Colonización por Pneumocystis jirovecii en contactos de pacientes con neumocistosis: detección por técnicas moleculares. Estudio preliminar. Med Inter (Caracas). 2011;27(2):110–8 Available in: http://svmi.web.ve/wh/revista/V27_N2.pdf#page=36. Accesed 7 September, 2019. In this study the high sensitivity of nPCR allowsP. jiroveciidetection in a significant percentage of asymptomatic immunocompetent people. DIF and nPCR must be done together, for an adequate interpretation of the results, during the study of the potential carriers ofP. jirovecii.

    Google Scholar 

  51. Wang Y, Doucette S, Qian Q, Kirby E. Yield of primary and repeat induced sputum testing for Pneumocystis jirovecii in human immunodeficiency virus-positive and negative patients. Arch Pathol Lab Med. 2007;131:1582–4. https://doi.org/10.1043/1543-2165(2007)131[1582:YOPARI]2.0.CO;2.

    Article  PubMed  Google Scholar 

  52. Olson M, Stralin K, Holmberg H. Clinical significance of nested polymerase chain reaction and immunofluorescence for detection of Pneumocystis carinii pneumonia. Clin Microbiol Infect. 2001;7:492–7. https://doi.org/10.1046/j.1469-0691.2001.00309.x.

    Article  Google Scholar 

  53. Kaur R, Wadhwa A, Bhalla P, Dhakad MS. Pneumocystis pneumonia in HIV patients: a diagnostic challenge. Med Mycol. 2015;53:587–92. https://doi.org/10.1093/mmy/myv023.

    Article  CAS  PubMed  Google Scholar 

  54. •• Esteves F, Gaspar J, de Sousa B, Antunes F, Mansinho K, Matos O. Pneumocystis jirovecii multilocus genotyping in pooled DNA samples: a new approach for clinical and epidemiological studies. Clin Microbiol Infect. 2012;18:E177–84. https://doi.org/10.1111/j.1469-0691.2012.03828.xUsing qPCR followed by multiplex-PCR/single base extension (MPCR/SBE-DNA) pooling method, described in this study, has showed to be a useful high-throughput procedure for large-scale study ofP. jiroveciispecific single-nucleotide polymorphisms (SNPs) screening, and a powerful tool for evaluation of clinically relevant SNPs potentially related to parasite burden, clinical diagnosis and follow-up ofP. jiroveciiinfection.

    Article  CAS  PubMed  Google Scholar 

  55. •• Morilla R, González-Magaña A, Friaza V, de Armas Y, Medrano FJ, Calderón EJ, et al. Genetic polymorphisms of superoxide dismutase locus of Pneumocystis jirovecii in Spanish population. Front Public Health. 2019;7:292. https://doi.org/10.3389/fpubh.2019.00292The aim of this work was to provide information about the prevalence ofPneumocystisSOD genotypes among Spanish patients, and to describe possible differences between both colonized and PCP patients.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Wakefield AE, Pixley FJ, Banerji S, Sinclair K, Miller RF, Moxan ER, et al. Detection of Pneumocystis carinii with DNA amplification. Lancet. 1990;336:451–3. https://doi.org/10.1016/0140-6736(90)92008-6.

    Article  CAS  PubMed  Google Scholar 

  57. Robberts FJL, Liebowitz LD, Chalkley LJ. Polymerase chain reaction detection of Pneumocystis jiroveci: evaluation of 9 assays. Diagn Microbiol Infect Dis. 2007;58(4):385–92. https://doi.org/10.1016/j.diagmicrobio.2007.02.014.

    Article  CAS  PubMed  Google Scholar 

  58. Atzori C, Angeli E, Agostini F, Mainini A, Filippini M, Micheli V, et al. Emerging aspects related to the application of biomolecular techniques to the diagnosis of Pneumocystis carinii pneumonia: our experience with ITSs primers. FEMS Immun Med Microbiol. 1998;22:93–5. https://doi.org/10.1111/j.1574-695X.1998.tb01192.x.

    Article  CAS  Google Scholar 

  59. Sing A, Trebesius K, Roggenkamp A, Rüssmann H, Tybus K, Pfaff F, Bogner JR, Emminger C, Heesemann J. Evaluation of diagnostic value and epidemiological implications of PCR for Pneumocystis carinii in different immunosuppressed and immunocompetent patient groups. J Clin Microbiol. 2000;38:1461–1467. Available in: https://jcm.asm.org/content/jcm/38/4/1461.full-text.pdf. Accesed 7 June, 2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Nevez G, Raccurt C, Jounieaux V, Dei-Cas E, Mazars E. Pneumocystosis versus pulmonary Pneumocystis carinii colonization in HIV-negative and HIV positive patients. AIDS. 1999;13:535–536. Available in: https://journals.lww.com/aidsonline/Fulltext/1999/03110/Pneumocystosis_versus_pulmonary_Pneumocystis.20.aspx. Accesed 17 June 2019.

    Article  CAS  PubMed  Google Scholar 

  61. Walzer PD, Smulian AG, Miller R. Pneumocystis species. In: Bennett JE, Dolin JE, Blaser MJ, editors. Mandell, Douglas, and Bennett’s infectious disease essentials. Philadelphia, PA: Elsevier; 2017.

    Google Scholar 

  62. Latouche S, Rabodonirina M, Mazars E. Pneumocystis: the “carrier state”: epidemiology and transmission of human pneumocystosis. FEMS Immun Med Microbiol. 1998;22:81–6. https://doi.org/10.1016/S0928-8244(98)00058-3.

    Article  CAS  Google Scholar 

  63. Olsson M, Elvin K, Lofdahl S, Linder E. Detection of Pneumocystis carinii DNA in sputum and bronchoalveolar lavage samples by polymerase chain reaction. J Clin Microbiol. 1993;31:221–226. Available in: https://jcm.asm.org/content/jcm/31/2/221.full.pdf. Accesed 17 June, 2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lipschick GY, Gill VJ, Lungren JD, Kovacs JA, Gill VJ, Nelson NA, et al. Improved diagnosis of Pneumocystis carinii infection by polymerase chain reaction on induced sputum and blood. Lancet. 1992;340:203–6. https://doi.org/10.1016/0140-6736(92)90469-J.

    Article  Google Scholar 

  65. Moonens F, Liesnard C, Brancard F, Van Vooren JP, Serruys E. Rapid simple and nested polymerase chain reaction for the diagnosis of Pneumocystis carinii pneumonia. Scand J Infect Dis. 1995;27:358–62. https://doi.org/10.3109/00365549509032731.

    Article  CAS  PubMed  Google Scholar 

  66. Schluger N, Godwin T, Sepkowitz K, Armstrong D, Bernard E, Rifkin M, et al. Application of DNA amplification to pneumocystosis: presence of serum Pneumocystis carinii DNA during human and experimentally induced Pneumocystis carinii pneumonia. J Exp Med. 1992;176:1327–33. https://doi.org/10.1084/jem.176.5.1327.

    Article  CAS  PubMed  Google Scholar 

  67. Sepkowitz K, Schluger N, Godwin T, Armstrong D, Cerami A, Bucala R. DNA amplification in experimental pneumocystosis: characterization of serum Pneumocystis carinii DNA and potential P. carinii carrier states. J Infect Dis. 1993;168:421–6. https://doi.org/10.1093/infdis/168.2.421.

    Article  CAS  PubMed  Google Scholar 

  68. Davis JL, Welsh DA, Beard CB, Jones JL, Lawrence GG, Fox MR. Pneumocystis colonization is common among hospitalized HIV infected patients with non-Pneumocystis pneumonia. Thorax. 2008;63:329–34. https://doi.org/10.1136/thx.2007.088104.

    Article  CAS  PubMed  Google Scholar 

  69. Miller RF, Lindley AR, Copas A, Ambrose HE, Davies RJO, Wakefield AE. Genotypic variation in Pneumocystis jirovecii isolates in Britain. Thorax. 2005;60:679–82. https://doi.org/10.1136/thx.2004.039818.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Epstein LJ, Meyer RD, Antonson S, Strigle SM, Mohsenifar Z. Persistence of Pneumocystis carinii in patients with AIDS receiving chemoprophylaxis. Am J Respir Crit Care Med. 1994;150:1456–9. https://doi.org/10.1164/ajrccm.150.5.7952576.

    Article  CAS  PubMed  Google Scholar 

  71. Guo F, Chen Y, Yang S-L, Xia H, Li X-W, Tong Z-H. Pneumocystis pneumonia in HIV-infected and immunocompromised non-HIV infected patients: a retrospective study of two centers in China. PLoS One. 2014;9:e101943. https://doi.org/10.1371/journal.pone.0101943.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Helweg-Larsen J, Tsolaki AG, Miller RF, Lundgren B, Wakefield AE. Clusters of Pneumocystis carinii pneumonia: analysis of person-to-person transmission by genotyping. QJM. 1998;91:813–20. https://doi.org/10.1093/qjmed/91.12.813.

    Article  CAS  PubMed  Google Scholar 

  73. Barry SM, Johnson MA. Pneumocystis carinii pneumonia: a review of current issues in diagnosis and management. HIV Med. 2001;2:123–32. https://doi.org/10.1046/j.1468-1293.2001.00062.x.

    Article  CAS  PubMed  Google Scholar 

  74. Morris A, Lundgren JD, Masur H, Walzer PD, Hanson DL, Frederick T, et al. Current epidemiology of Pneumocystis pneumonia. Emerg Infect Dis. 2004;10:1713–20. https://doi.org/10.3201/eid1010.030985.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Morris A, Sciurba FC, Norris KA. Pneumocystis: a novel pathogen in chronic obstructive pulmonary disease? COPD. 2008;5:43–51a. https://doi.org/10.1080/15412550701817656.

    Article  PubMed  Google Scholar 

  76. •• Vidal S, de la Horra C, Martín J, Montes-Cano MA, Rodríguez E, Respaldiza N. Pneumocystis jirovecii colonization in patients with interstitial lung disease. Clin Microbiol Infect. 2006;12:231–5. https://doi.org/10.1111/j.1469-0691.2005.01337.xThis prospective study was conducted to determine prevalence of colonization byP. jiroveciiin patients who required bronchoscopy and BAL, following suspicion of interstitial lung disease (ILD). The high prevalence ofP. jiroveciicarriers found among immunocompetent patients with ILDs in Spain suggests a possible role ofP. jiroveciiin the natural history of these diseases.

    Article  CAS  PubMed  Google Scholar 

  77. Helwed-Larsen J, Skov Jensen J, Dohn B, Benfield TL, Lundgren B. Detection of Pneumocystis DNA in samples from patients suspected of bacterial pneumonia – a case – control study. BMC Infect Dis. 2002;2(28). https://doi.org/10.1186/1471-2334-2-28.

  78. Visconti E, Marinaci S, Zolfo M, Mencarini P, Tamburrini E. Very low frequency of Pneumocystis carinii DNA detection by PCR in specimens from patients with lung damage. J Clin Microbiol. 2000;38:1307–1308. Available in: https://jcm.asm.org/content/jcm/38/3/1307.full.pdf. Accesed 7 June, 2019.

  79. Strutt M, Smith M. Development of a real-time probe-based PCR assay for the diagnosis of Pneumocystis pneumonia. Med Mycol. 2005;43:343–7. https://doi.org/10.1080/13693780412331282340.

    Article  CAS  PubMed  Google Scholar 

  80. Armbruster C, Hassl A, Kriwanek S. Pneumocystis carinii colonization in the absence or immunosuppression. Scand J Infect Dis. 1997;29:591–3. https://doi.org/10.3109/00365549709035900.

    Article  CAS  PubMed  Google Scholar 

  81. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–21. https://doi.org/10.1086/588660.

    Article  PubMed  Google Scholar 

  82. Donelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis. 2019; ciz1008. doi: https://doi.org/10.1093/cid/ciz1008.

  83. Ayats J, Martín-Mazuelos E, Pemán J, Quindós G, Sanchez F, García-Rodriguez J, et al. Recomendaciones sobre el diagnóstico de la enfermedad fúngica invasora de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC). Actualización 2010. Enferm Infecc Microbiol Clin. 2011;29(1):39.e1–39.e15. https://doi.org/10.1016/j.eimc.2010.08.005.

    Article  Google Scholar 

  84. Probst M, Ries H, Schmidt-Wieland T, Serr A. Detection of Pneumocystis carinii DNA in patients with chronic lung diseases. Eur J Clin Microbiol Infect Dis. 2000;19:644–5. https://doi.org/10.1007/s100960000329.

    Article  CAS  PubMed  Google Scholar 

  85. Roblot F, Le Moal G, Godet C, Hutin P, Texereau M, Boyer E, et al. Pneumocystis carinii pneumonia in patients with hematologic malignancies: a descriptive study. J Inf Secur. 2003;47:19–27. https://doi.org/10.1016/S0163-4453(03)00038-0.

    Article  CAS  Google Scholar 

  86. Roux N, Flipo RM, Cortet B, Lafitte JJ, Tonnel AB, Duquesnoy B, et al. Pneumocystis carinii pneumonia in rheumatoid arthritis patient treated with methotrexate. A report of two cases. Rev Rhum Engl Ed. 1996;63:453–6.

    CAS  PubMed  Google Scholar 

  87. Sepkowitz KA, Brown AE, Telzak EE, Gottlieb S, Armstrong D. Pneumocystis carinii pneumonia among patients without AIDS at a cancer hospital. JAMA. 1992;267:832–7. https://doi.org/10.1001/jama.1992.03480060078034.

    Article  CAS  PubMed  Google Scholar 

  88. Gits-Muselli M, White PL, Mengoli C, Chen S, Crowley B, Dingemans G, et al. The Fungal PCR Initiative’s evaluation of in-house and commercial Pneumocystis jirovecii qPCR assays: toward a standard for a diagnostics assay. Med Mycol. 2019; myz115. doi: https://doi.org/10.1093/mmy/myz115.

  89. •• Matos O, Tomás AL, Antunes F. Pneumocystis jirovecii and PcP. In: Current Progress in Medical Mycology. Cham: Springer International Publishing; 2017. p. 215–54. This chapter presents a balanced, comprehensive, and concise examination of the latest advances in the field ofP. jiroveciipneumonia, and contains the most up-to-date references.

    Book  Google Scholar 

  90. Huggett JF, Taylor MS, Kocjan G, Evans HE, Morris-Jones S, Gant V, et al. Development and evaluation of a real-time PCR assay for detection of Pneumocystis jirovecii DNA in bronchoalveolar lavage fluid of HIV-infected patients. Thorax. 2008;63(2):154–9. https://doi.org/10.1136/thx.2007.081687.

    Article  CAS  PubMed  Google Scholar 

  91. Azoulay E, Bergeron A, Chevret S, Bele N, Schlemmer B, Menotti J. Polymerase chain reaction for diagnosing Pneumocystis pneumonia in non-HIV immunocompromised patients with pulmonary infiltrates. Chest. 2009;135(3):655–61. https://doi.org/10.1378/chest.08-1309.

    Article  CAS  PubMed  Google Scholar 

  92. Denning DW. The burden of serious fungal infections in Latin America. Global Fungal Infection Forum 4. Available in: https://life-slides-and-videos.s3.eu-west-2.amazonaws.com/LIFE+articles/Burden+of+serious+fungal+infections+in+Latin+America.pdf. Accesed 5 November, 2019.

  93. Limper A, Adenis A, Le T, Harrison S. Fungal infections in HIV/AIDS. Lancet Infect Dis. 2017;17(11):e334–43. https://doi.org/10.1016/S1473-3099(17)30303-1.

    Article  PubMed  Google Scholar 

  94. Denning D. Minimizing fungal disease deaths will allow the UNAIDS target of reducing annual AIDS deaths below 500 000 by 2020 to be realized. Trans R Soc B London Biol Sci. 2016;371(1709):20150468. https://doi.org/10.1098/rstb.2015.0468.

    Article  Google Scholar 

  95. Cortés-Télles A, Juarez F, Peña E. Neumonía por Pneumocystis jirovecii en pacientes con VIH. Neumol Cir Torax. 2011;70(3):165–171. Available in: https://www.medigraphic.com/pdfs/neumo/nt-2011/nt113e.pdf. Accesed 7 September, 2019.

  96. Prado M, Barbosa M, Laurenti R, Travassos L, Taborda C. Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006. Mem Inst Oswaldo Cruz. 2009;104(3):513–21. https://doi.org/10.1590/S0074-02762009000300019.

    Article  PubMed  Google Scholar 

  97. Risquez A, Traslaviña F, Wannes A, Yepez P, Zafra P, Rodríguez A. Mortalidad por infección VIH/SIDA en Venezuela, 1996–2007. Gac Med Caracas 2011; 119(3):188–198. Available in: http://www.anm.org.ve/anm/cms/svcobtenerpdfrevista.php?id=0000000016&tipo=normal&fila=7. Accesed 5 September, 2019.

  98. Lemus-Espinoza D, Maniscalchi Badaoui MT, Sigona-Giangreco I, Wahab F. Mortalidad por micosis sistémicas asociadas a la infección por VIH en Venezuela. Período 1996-2013. Investig Clin. 2019;60(2):171–81. https://doi.org/10.22209/IC.v60n2a06.

    Article  Google Scholar 

  99. Lowe DM, Rangaka MX, Gordon F, James CD, Miller RF. Pneumocystis jirovecii pneumonia in tropical and low and middle income countries: a systematic review and meta-regression. PLoS One. 2013;8(8):e69969. https://doi.org/10.1371/journal.pone.0069969.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Lemus-Espinoza D, Maniscalchi MT, Wahab F, Sigona I. Mortalidad por micosis sistémicas no asociadas a VIH, en Venezuela. Período 1995-2013. Investig Clin. 2018;59(2):107–17. https://doi.org/10.22209/IC.v59n2a01.

    Article  Google Scholar 

  101. Lopes A, Tobon A, Restrepo A, Queiroz F, Nucci M. Epidemiology of endemic systemic fungal infections in Latin America. Med Mycol. 2011;49(8):1–19. https://doi.org/10.3109/13693786.2011.577821.

    Article  Google Scholar 

  102. Dei-Cas E. Pneumocystis infections: the iceberg? Med Mycol. 2000;38(Supp1):23–32. https://doi.org/10.1080/mmy.38.s1.23.32.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We want to thank to all members of IBEROPNEUMOCYSTIS, especially Olga Matos (Universidade NOVA de Lisboa) and Carmen de La Horra and Vicente Friaza (Instituto de Biomedicina de Sevilla, España), for their support and friendship. We also want to thank David Denning and Ana Alastruey-Izquierdo for their support and Lieska Rodríguez, Manager of Diagnosis and Epidemiological Surveillance of Rafael Rangel National Institute of Hygiene.

Venezuelan Group for the Study of Pneumocystosis

María Mercedes Panizo, Giuseppe Ferrara, and Nataly García (were part of the group of the Instituto Nacional de Higiene Rafael Rangel until May 2019); Vera Reviakina and Maribel Dolande (currently retired professionals from the Instituto Nacional de Higiene Rafael Rangel); Víctor Alarcón (Instituto Nacional de Higiene Rafael Rangel); Xiomara Moreno and Ana María Cáceres (Instituto Médico La Floresta); Trina Navas (Hospital General del Oeste Dr. José Gregorio Hernández); Enrique Calderon is the coordinator of the Iberoamerican Pneumocystis Network (IBEROPNEUMOCYSTIS). Maria Mercedes Panizo was the leader of the Venezuelan group.

Author information

Authors and Affiliations

  1. Sociedad Venezolana de Microbiología, Caracas, Venezuela

    María Mercedes Panizo

  2. Laboratorio de Referencia Referlab, Caracas, Venezuela

    Giuseppe Ferrara & Nataly García

  3. Instituto Médico La Floresta, Caracas, Venezuela

    Xiomara Moreno

  4. Hospital General del Oeste Dr. José Gregorio Hernández, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela

    Trina Navas

  5. Centro de Investigación Biomédica en Red (CIBER) de Epidemiología y Salud Pública/Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain

    Enrique Calderón

Authors
  1. María Mercedes Panizo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giuseppe Ferrara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nataly García
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiomara Moreno
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Trina Navas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Enrique Calderón
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the Venezuelan Group for the Study of Pneumocystosis belonging to the Iberoamerican Pneumocystosis Network (IBEROPNEUMOCYSTIS)

Corresponding author

Correspondence to María Mercedes Panizo.

Ethics declarations

Conflict of Interest

María Mercedes Panizo, Giuseppe Ferrara, Nataly García, Xiomara Moreno, Trina Navas, and Enrique Calderón 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.

Additional information

This article is part of the Topical Collection on Clinical Mycology Lab Issues (S Cordoba, Section Editor)

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Panizo, M.M., Ferrara, G., García, N. et al. Diagnosis, Burden and Mortality of Pneumocystis jirovecii Pneumonia in Venezuela. Curr Fungal Infect Rep 14, 29–39 (2020). https://doi.org/10.1007/s12281-020-00377-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12281-020-00377-4

Keywords

Search

Navigation