Risk of Pneumocystis jiroveci pneumonia in patients long after renal transplantation.

BACKGROUND Pneumocystis jiroveci pneumonia (PCP) is an important cause of morbidity and mortality in renal transplant recipients (RTRs). Chemoprophylaxis with trimethoprim/sulphamethoxazole is recommended during the early post-transplantation period, but the optimal duration has not been determined and a main drawback of chemoprophylaxis is the development of resistance of the commensal faecal flora. A cluster outbreak of PCP occurred in our outpatient Renal Transplant Unit. We aimed to investigate risk factors for PCP in RTRs to determine who should receive long-term chemoprophylaxis. METHODS In a case-control study, we investigated common demographic variables and immunological parameters. Nine PCP cases diagnosed between August 2006 and April 2007 were matched with 18 control patients, who did not develop PCP, received their transplant in the same time-period and had a similar follow-up period with a comparable immunosuppressive drug regimen. RESULTS The median time from transplantation to PCP was 19 months. We observed no significant differences in gender, age, donor type or number of rejections. In PCP cases, the median lymphocyte count just before PCP diagnosis was 0.49 (0.26-0.68), which was significantly reduced compared to the control patients after a similar follow-up period (median 1.36, 0.59-3.04, P = 0.002). This lymphocytopaenia was chronic and existed in most patients already for many months. CD4(+) T-cell counts were also significantly reduced in the PCP cases. We found no difference in the Th1, Th2 and Th17 subsets between PCP cases and control patients. CONCLUSION Long-term prophylactic therapy for PCP may be indicated for RTR with persistent severe lymphocytopaenia.

[1]  F. Baas,et al.  Molecular profiling of cytomegalovirus-induced human CD8+ T cell differentiation. , 2010, The Journal of clinical investigation.

[2]  R. Porcher,et al.  Pneumocystis jirovecii pneumonia in renal transplant recipients occurring after discontinuation of prophylaxis: a case–control study , 2010 .

[3]  Ethan M Balk,et al.  KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary. , 2010, Kidney international.

[4]  S. Cohney,et al.  Late onset Pneumocystis pneumonia in patients receiving rituximab for humoral renal transplant rejection , 2009, Nephrology.

[5]  H. Yazaki,et al.  Outbreak of Pneumocystis jiroveci Pneumonia in Renal Transplant Recipients: P. jiroveci Is Contagious to the Susceptible Host , 2009, Transplantation.

[6]  J. Kovacs,et al.  Evolving health effects of Pneumocystis: one hundred years of progress in diagnosis and treatment. , 2009, JAMA.

[7]  John T Brooks,et al.  Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. , 2009, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[8]  W. Hörl,et al.  Late onset Pneumocystis pneumonia in renal transplantation after long‐term immunosuppression with belatacept , 2009, Transplant infectious disease : an official journal of the Transplantation Society.

[9]  Deepali Kumar,et al.  Pneumocystis jirovecii pneumonia after rituximab therapy for antibody‐mediated rejection in a renal transplant recipient , 2009, Transplant infectious disease : an official journal of the Transplantation Society.

[10]  T. Yong,et al.  Late-onset and atypical presentation of Pneumocystis carinii pneumonia in a renal transplant recipient , 2009, Clinical and Experimental Nephrology.

[11]  J. Heesemann,et al.  Molecular Evidence of Nosocomial Pneumocystis jirovecii Transmission among 16 Patients after Kidney Transplantation , 2008, Journal of Clinical Microbiology.

[12]  J. Fishman,et al.  Infection in Renal Transplant Recipients , 2007, Kidney Transplantation.

[13]  H. V. van Houwelingen,et al.  An outbreak of Pneumocystis jiroveci pneumonia with 1 predominant genotype among renal transplant recipients: interhuman transmission or a common environmental source? , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  J. Shellito,et al.  Interleukin-23 (IL-23)-IL-17 Cytokine Axis in Murine Pneumocystis carinii Infection , 2007, Infection and Immunity.

[15]  P. Vanhems,et al.  Molecular Evidence of Interhuman Transmission of Pneumocystis Pneumonia among Renal Transplant Recipients Hospitalized with HIV-Infected Patients , 2004, Emerging infectious diseases.

[16]  Blackwell Munksgaard.  Pneumocystis jiroveci (formerly Pneumocystis carinii) , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[17]  C. Beard,et al.  Pneumocystis Colonization in HIV‐Infected Patients , 2003, The Journal of eukaryotic microbiology.

[18]  R. Lattes,et al.  Risk factors for Pneumocystis carinii pneumonia in kidney transplant recipients: a case–control study , 2003, Transplant infectious disease : an official journal of the Transplantation Society.

[19]  K. Sepkowitz.  Opportunistic infections in patients with and patients without Acquired Immunodeficiency Syndrome. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  Robert F Miller,et al.  Pneumocystis carinii f. sp. hominisDNA in Immunocompetent Health Care Workers in Contact with Patients with P. carinii Pneumonia , 2001, Journal of Clinical Microbiology.

[21]  W. Hughes.  Pneumocystis Carinii Pneumonia * , 2001, Interstitial Lung Diseases in Children.

[22]  C. Cabrera,et al.  Search for primary infection by Pneumocystis carinii in a cohort of normal, healthy infants. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[23]  R. Garland,et al.  Peripheral blood CD4 + T-lymphocyte counts during Pneumocystis carinii pneumonia in immunocompromised patients without HIV infection. , 2000, Chest.

[24]  Pascal Vincent,et al.  Pulmonary colonization with Pneumocystis carinii in human immunodeficiency virus-negative patients: assessing risk with blood CD4+ T cell counts. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[25]  Lundgren,et al.  Pneumocystis carinii major surface glycoprotein induces interleukin‐8 and monocyte chemoattractant protein‐1 release from a human alveolar epithelial cell line , 1999, European journal of clinical investigation.

[26]  A. Arroliga,et al.  Should prophylaxis for Pneumocystis carinii pneumonia in solid organ transplant recipients ever be discontinued? , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[27]  Sheldon,et al.  Pneumocystis carinii induces interleukin 6 production by an alveolar epithelial cell line , 1998, European journal of clinical investigation.

[28]  R. Garland,et al.  Use of adjunctive corticosteroids in severe adult non-HIV Pneumocystis carinii pneumonia. , 1998, Chest.

[29]  J. Standing,et al.  The role of alveolar macrophages in Pneumocystis carinii degradation and clearance from the lung. , 1997, The Journal of clinical investigation.

[30]  J. Vandenbroucke,et al.  Rejection treatment and cytomegalovirus infection as risk factors for Pneumocystis carinii pneumonia in renal transplant recipients. , 1996, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[31]  A. Hoitsma,et al.  Pneumocystis carinii pneumonia in renal transplant recipients. , 1995, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[32]  F. Emmrich,et al.  CYTOMEGALOVIRUS INFECTION IN TRANSPLANT RECIPIENTS THE ROLE OF TUMOR NECROSIS FACTOR , 1994, Transplantation.

[33]  E. Hardy,et al.  CD4 T-lymphocyte counts as predictors of pneumonia after kidney transplantation. , 1993, Transplantation proceedings.

[34]  E. Eden,et al.  Correlation of bronchoalveolar lavage findings to severity of Pneumocystis carinii pneumonia in AIDS. Evidence for the development of high-permeability pulmonary edema. , 1992, Chest.

[35]  P. Francioli,et al.  Transmission of Pneumocystis carinii from AIDS patients to other immunosuppressed patients: a cluster of Pneumocystis carinii pneumonia in renal transplant recipients. , 1991, AIDS.

[36]  J. Shellito,et al.  A new model of Pneumocystis carinii infection in mice selectively depleted of helper T lymphocytes. , 1990, The Journal of clinical investigation.

[37]  J. Bernaudin,et al.  Cell population obtained by bronchoalveolar lavage in Pneumocystis carinii pneumonitis. , 1985, Acta cytologica.

[38]  European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.7.1 Late infections. Pneumocystis carinii pneumonia. , 2002, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[39]  F. Berthoux.  SECTION IV: Long-term management of the transplant recipient , 2002 .

[40]  Ebpg.  European Best Practice Guidelines for Renal Transplantation (part 1). , 2000, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.