Pneumocystis jirovecii in HIV patients and suspected pneumonia: a problematic diagnosis in Caracas, Venezuela. / Pneumocystis jirovecii en pacientes con infección por el VIH y sospecha de neumonía: un diagnóstico problemático en Caracas, Venezuela.

  • María Mercedes Panizo Instituto Nacional de Higiene Rafael Rangel
  • Giuseppe Ferrara Instituto Nacional de Higiene Rafael Rangel
  • Nataly García Instituto Nacional de Higiene Rafael Rangel
  • Vera Reviakina Instituto Nacional de Higiene Rafael Rangel
  • Trina Navas Hospital General del Oeste Dr. José Gregorio Hernández
  • Xiomara Moreno Instituto Médico La Floresta
  • Ana María Capote Instituto Nacional de Higiene Rafael Rangel
  • Maribel Dolande
  • Víctor Alarcón Instituto Nacional de Higiene Rafael Rangel
  • Enrique Calderón Instituto de Biomedicina de Sevilla
Palabras clave: AIDS, direct immunofluorescence, HIV infection, nested PCR, Pneumocystis jirovecii, SIDA, inmunofluorescencia directa, infección por VIH, PCR anidada, Pneumocystis jirovecii.

Resumen

Abstract.

Pneumocystis jirovecii pneumonia (PCP) is one of the most frequent opportunistic infections in immunocompromised patients. The objective of this study was to know the P. jirovecii epidemiology in Venezuelan patients with Human Immunodeficiency Virus (HIV) infection and suspected pneumonia, through passive surveillance at a national reference laboratory during six years. Laboratory records of patients with HIV infection, who were hospitalized with acute lower respiratory tract infection (ALRTI), and presumptive clinical diagnosis of PCP, were reviewed between January 2007 and December 2012, at the Mycology Department of the Instituto Nacional de Higiene Rafael Rangel. Several respiratory specimens were received and the direct immunofluorescence assay (DIF) and nested polymerase chain reaction (nPCR) diagnostic techniques were used. One hundred and sixty-one respiratory samples were processed and P. jirovecii was detected in 76 samples by DIF and in 20 by nPCR. PCP’s frequency in Venezuelan patients with HIV is high and it has been sustained throughout time. Colonization by P. jirovecii has uncertain clinical significance, but this study provides evidence that the state of advanced immunosuppression increases the probability of colonization. DIF and nPCR are very useful techniques for PCP diagnosis, but are of limited access in many hospital centers, especially in developing countries. We recommend the use of DIF with spontaneous sputum specimens as the first diagnostic line for PCP in patients with HIV infection. The results obtained by nPCR should be interpreted with caution, taking into account the patient’s clinical symptoms.

Resumen.

La neumonía por Pneumocystis jirovecii (PCP) es una de las infecciones oportunistas más frecuente en pacientes inmunocomprometidos. El objetivo de este trabajo fue conocer la epidemiología del P. jirovecii en pacientes venezolanos con infección por el Virus de Inmunodeficiencia Humana (VIH) y sospecha de neumonía, mediante vigilancia pasiva en un laboratorio de referencia nacional durante un período de 6 años. Se revisaron los registros de laboratorio de los pacientes con infección por el VIH hospitalizados con Infección Aguda del Tracto Respiratorio Inferior (IATRI) y diagnóstico clínico presuntivo de PCP, entre enero de 2007 a diciembre de 2012 en el Departamento de Micología del Instituto Nacional de Higiene Rafael Rangel. Se recibieron diversas muestras del tracto respiratorio y los métodos diagnósticos empleados fueron inmunofluorescencia directa (IFD) y reacción en cadena de la polimerasa anidada (nPCR). Se procesaron 161 muestras respiratorias y se detectó P. jirovecii en 76 muestras por IFD y en 20 por nPCR. La frecuencia de PCP en pacientes venezolanos con HIV es elevada y se ha mantenido en el tiempo. La colonización por P. jirovecii tiene un significado clínico incierto, pero este estudio aporta evidencia de que un estado avanzado de inmunosupresión incrementa la probabilidad de colonización. La IFD y la nPCR son técnicas muy útiles para el diagnóstico de la PCP, pero son de acceso limitado en muchos centros hospitalarios, sobre todo en países en vías de desarrollo. Recomendamos la utilización de la IFD con muestras de esputo espontáneo como primera línea de diagnóstico para la PCP en pacientes con VIH. Los resultados obtenidos por nPCR deben ser interpretados tomando en cuenta la sintomatología clínica del paciente.

Citas

Choe PG, Kang YM, Kim G, Park WB, Park SW, Kim HB, Oh M, Chong Kim E, Kim NJ. Diagnostic value of direct fluorescence antibody staining for detecting Pneumocystis jirovecii in expectorated sputum from patients with HIV infection. Med Mycol 2014; 52: 326-330. doi: https://doi.org/10.1093/ mmy/myu002.

Kaur R, Wadhwa A, Bhalla P, Dhakad MS. Pneumocystis pneumonia in HIV patients: a diagnostic challenge. Med Mycol 2015; 53: 587-592. doi: https://doi.org/10.1093/ mmy/myv023.

Siegel M, Masur H, Kovacs J. Pneumocystis jirovecii pneumonia in human immunodeficiency infection. Semin Respir Crit Care Med 2016; 37: 243-256. doi: https:// doi.org/10.1055/s-0036-1579556.

Borelli K, Brito A, Rivas G, Panizo MM, Roldán Y. Diagnóstico de Pneumocystis carinii: Estudio comparativo entre inmunofluorescencia directa y la colo- ración histológica de Gomori-Grocott. Bol Soc Ven Microbiol 2000; 20: 46-52. Available from: http://ve.scielo.org/scie- lo.php?script=sci_arttext&pid=S1315- 25562000000100010&lng=es&nrm=iso& tlng=es. Accesed 5 July, 2019.

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: 982-989. doi: http:// doi.org/10.1183/09031936.02.01372002.

Panizo MM, Reviakina V, Navas T, Casa- nova K, Sáez A, Guevara RN, Cáceres AM, Vera R, Sucre C, Arbona E. Neumocistosis en pacientes venezolanos: diagnóstico y epidemiología (2001-2006). Rev Iberoam Micol 2008; 25: 226-231. doi: https://doi. org/10.1016/S1130-1406(08)70054-8.

Panizo MM, Alarcón V, Reviakina V, Navas T. Evaluación de la técnica de PCR anida- da para el diagnóstico de Pneumocystis jirovecii. Rev Soc Ven Microbiol 2009; 29: 136-139. Available from: http://ve.scielo. org/pdf/rsvm/v29n2/art13.pdf. Accesed 7 July, 2019.

Tomás AL, Matos O. Pneumocystis jirovecii pneumonia: current advances in la- boratory diagnosis. OBM Genetics 2018; 2(4). https://doi.org/10.21926/obm.genet. 1804049.

Casanova K, Sáez A, Navas T, Reviakina V, Panizo M, Chiriboga D. Epidemiolo- gía de la neumocistosis. Med Interna (Ca- racas) 2006; 22(3): 207-226. Available from: http://svmi.web.ve/wh/revista/V22_ N3.pdf. Accesed 17 October, 2019.

Cermeño J R. Hernández de Cuesta I, Alcalá F, Áppice M. Pneumocystis jirovecii en centros hospitalarios del Estado Bolívar, Venezuela. Rev Biomed 2006; 17: 169-174. doi: https:// doi.org/10.32776/revbiomed.v17i3.454.

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: 565-570. doi: https://doi.org/10.1586/ eri.13.41.

De Armas Rodríguez Y, Wissmann G, Müller AL, Pederiva MA, Brum MC, Brack- mann RL, Capó De Paz V, Calderón EJ. Pneumocystis jirovecii pneumonia in developing countries. Parasite 2011; 18: 219-228. doi: http://doi.org/10.1051/parasi- te/2011183219.

Wakefield AE, Pixley FJ, Banerji S, Sinclair K, Miller RF, Moxan ER, Hopkin JM. Detection of Pneumocystis carinii with DNA amplification. Lancet 1990; 336: 451-453. doi: https://doi.org/10.1016/0140-6736(90)92008-6.

Wakefield AE, Guiver L, Miller RF, Hopkin JM. DNA amplification on induced sputum samples for diagnosis of Pneumocystis carinii pneumonia. Lancet 1991; 337: 1378-1379. doi: https://doi.org/10.1016/0140- 6736(91)93062-E.

Alvarez-Martínez MJ, Moreno A, Miró JM, Valls ME, Rivas PV, de Lazzaria E, Sued O, Benito N, Domingo P, Ribera E, Santín M, Sirera G, Segura F, Vidal F, Rodríguez F, Riera M, Cordero ME, Arribas JR, Jiménez de Anta MT, Gatell JM, Wilson PE, Meshnick SR, Spanish PCP

Working Group. Pneumocystis jirovecii pneumonia in Spanish HIV-infected patients in the combined antiretroviral therapy era: prevalence of dihydropteroate synthase mutations and prognostic factors of mortality. Diag Microbiol Infec Dis 2008; 62: 34-43. doi: https://doi.org/10.1016/j.diagmicro- bio.2008.04.016.

Roux A, Canet E, Valade S, Gangneux-Robert F, Hamane S, Lafabrie A, Maubon D, Debourgogne A, Le Gal S, Dalle F, Leterrier M, Toubas D, Pomares C, Bellanger AP, Bonhomme J, Berry A, Durand-Joly I, Magne D, Pons D, Hennequin C, Maury E, Roux P, Azoulay É. Pneumocystis jirovecii pneumonia in patients with or without AIDS, France. Emerg Infect Dis 2014; 20: 1490-1497. doi: http://doi.org/10.3201/ eid2009.131668.

Ebner L, Walti LN, Rauch A, Furrer H, Cusini A, Meyer AMJ, Weiler S, Huynh-Do U, Heverhagen J, Arampatzis S, Christe Clinical course, radiological manifestations, and outcome of Pneumocystis jiro- vecii pneumonia in HIV patients and renal transplant recipients. PLoS ONE 2016; 11:e0164320. doi: https://doi.org/10.1371/ journal.pone.0164320.

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. doi: https://doi.org/10.1371/ journal.pone.0101943.

Du Plessis D, Poonsamy B, Msimang V, Davidsson L, Cohen C, Govender N, Dawoo- de H, Karstaedtcf A, Frean J. Laboratory- based surveillance of Pneumocystis jirovecii pneumonia in South Africa, 2006-2010. South Afr J Infect Dis 2016; 31: 8-13. doi: https://doi.org/10.1080/23120053.2015.1 118828.

The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Is it safe to discontinue primary Pneumocystis jiroveci pneumonia prophylaxis in patients with virologically suppressed HIV infection and a CD4 cell count <200 cells/µL? Clin Infect Dis 2010; 51(5): 611-619. doi: https://doi. org/10.1086/655761.

Pinlaor S, Mootsikapum P, Pinlaor P, Phunmanee A, Pipitgool V, Sithithaworn P, Chumpia W, Sithithaworn J. PCR diagnosis of Pneumocystis carinii sputum and bronchoalveolar lavage samples in immune compromised patients. Parasitol Res 2004; 94: 213-218. doi: https://doi.org/10.1007/ s00436-004-1200-y.

Lipschick GY, Gill VJ, Lungren JD, Kova- cs JA, Gill VJ, Nelson NA, Lundgren JD, Nielsen JO. Improved diagnosis of Pneumo- cystis carinii infection by polymerase chain reaction on induced sputum and blood. Lancet 1992; 340: 203-206. doi: https:// doi.org/10.1016/0140-6736(92)90469-J.

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 from: https:// jcm.asm.org/content/jcm/31/2/221.full. pdf. Accesed 17 June, 2019.

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: 358-362. doi: https:// doi.org/10.3109/00365549509032731.

Rabodonirina M, Raffenot D, Cotte L, Boibieux A, Mayençon M, Bayle G, Persat F, Rabatel F, Trepo C, Peyramond D, Piens MA. 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 from: https://jcm. asm.org/content/jcm/35/11/2748.full.pdf. Accesed 15 June, 2019.

Schluger N, Godwin T, Sepkowitz K, Armstrong D, Bernard E, Rifkin M, Cerami A, Bucala R. 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: 1327-1333. doi: https://doi.org/10.1084/jem.176.5.1327.

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: 421-426. doi: https://doi.org/10.1093/infdis/168.2.421.

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: 329-334. doi: http://dx.doi.org/10.1136/ thx.2007.088104.

Miller RF, Lindley AR, Copas A, Ambrose HE, Davies RJO, Wakefield AE. Genotypic variation in Pneumocystis jirovecii isolates in Britain. Thorax 2005; 60: 679-682. doi: http://dx.doi.org/10.1136/ thx.2004.039818.

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: 1456-1459. doi: https:// doi.org/10.1164/ajrccm.150.5.7952576.

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: 813-820. doi: https:// doi.org/10.1093/qjmed/91.12.813.

Leigh TR, Kangro HO, Gazzard BG, Je- ffries DJ, Collins JV. DNA amplification by the polymerase chain reaction to detect subclinical Pneumocystis carinii colonization in HIV-positive and HIV negative homosexuals with and without respiratory symptoms. Respir Med 1993; 87: 525-529. doi: https://doi.org/10.1016/0954- 6111(93)90008-N.

Huang L, Crothers K, Morris A, Groner G, Fox M, Turner JR, Merrifield C, Eiser S, Zucchi P, Beard CB. Pneumocystis colonization in HIV-infected patients. J Eukaryot Microbiol 2003; 50: 616-617. doi: https://doi . or g /10. 1111/j . 1550- 7408. 2003. tb00651.x.

Masur H, Ognibene FP, Yarchoan R, Shel- hamer J, Baird B, Travis W, Suffredini AF, Deyton L, Kovacs JA, Falloon J, Davey R, Polis M, Metcalf J, Baseler M, Wesley R, Gill VJ, Fauci AS, Lane HC. CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection. Ann Intern Med 1989; 111:223-231. doi: https://doi.org/10.1059/0003-4819-111-3-223.

Lugo L, Miquilareno M, Figueredo A, Silva M, Rodríguez Morales AJ. Respuesta a la terapia antirretroviral altamente activa en pacientes de 50 años de edad o más viviendo con infección VIH/SIDA. Gac Med Cara- cas 2012; 120(4): 292-301. Available from: http://www.anm.org.ve/anm/saciverrevista.php. Accesed April 22, 2019.

Randall Curtis J, Paauw DS, Wenrich MD, Carline JD, Ramsey PG. Ability of primary care physicians to diagnose and manage Pneumocystis carinii pneumonia. J Gen In- tern Med 1995; 10: 395-399. doi: https:// doi.org/10.1007/BF02599841.

Elstein AS, Schwarz A. Clinical problem solving and diagnostic decision making: selective review of the cognitive literature. BMJ 2002; 324: 729-732. doi: https://doi. org/10.1136/bmj.324.7339.729.

Navas Blanco TM. Micología clínica: la nece- sidad de una nueva visión. Med Interna (Ca- racas) 2015; 31(4): 163-166. Available from: http://www.svmi.web.ve/ojs/index.php/me- dint/article/view/11. Accesed April 22, 2019.

Publicado
2021-01-13
Sección
Trabajos Originales