An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients

Nina Singh, Olivier Lortholary, Barbara D. Alexander, Krishan L. Gupta, George T. John, Kenneth Pursell, Patricia Munoz, Goran B. Klintmalm, Valentina Stosor, Ramon Del Busto, Ajit P. Limaye, Jyoti Somani, Marshall Lyon, Sally Houston, Andrew A. House, Timothy L. Pruett, Susan Orloff, Atul Humar, Lorraine Dowdy, Julia Garcia-DiazAndre C Kalil, Robert A. Fisher, Shahid Husain

Research output: Contribution to journalArticle

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Abstract

Background. We describe an immune reconstitution syndrome (IRS)-like entity in the course of evolution of Cryptococcus neoformans infection in organ transplant recipients. Methods. The study population comprised a cohort of 83 consecutive organ transplant recipients with cryptococcosis who were observed for a median of 2 years in an international, multicenter study. Results. In 4 (4.8%) of the 83 patients, an IRS-like entity was observed a median of 5.5 weeks after the initiation of appropriate antifungal therapy. Worsening of clinical manifestations was documented, despite cultures being negative for C. neoformans. These patients were significantly more likely to have received tacrolimus, mycophenolate mofetil, and prednisone as the regimen of immunosuppressive therapy than were all other patients (P = .007). The proposed basis of this phenomenon is reversal of a predominantly Th2 response at the onset of infection to a Th1 proinflammatory response as a result of receipt of effective antifungal therapy and a reduction in or cessation of immunosuppressive therapy. Conclusions. This study demonstrated that an IRS-like entity occurs in organ transplant recipients with C. neoformans infection. Furthermore, this entity may be misconstrued as a failure of therapy. Immunomodulatory agents may have a role as adjunctive therapy in such cases.

Original languageEnglish (US)
Pages (from-to)1756-1761
Number of pages6
JournalClinical Infectious Diseases
Volume40
Issue number12
DOIs
StatePublished - Jun 15 2005

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Immune Reconstitution Inflammatory Syndrome
Cryptococcus neoformans
Transplants
Infection
Immunosuppressive Agents
Therapeutics
Mycophenolic Acid
Cryptococcosis
Tacrolimus
Prednisone
Multicenter Studies
Transplant Recipients
Population

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Singh, N., Lortholary, O., Alexander, B. D., Gupta, K. L., John, G. T., Pursell, K., ... Husain, S. (2005). An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients. Clinical Infectious Diseases, 40(12), 1756-1761. https://doi.org/10.1086/430606

An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients. / Singh, Nina; Lortholary, Olivier; Alexander, Barbara D.; Gupta, Krishan L.; John, George T.; Pursell, Kenneth; Munoz, Patricia; Klintmalm, Goran B.; Stosor, Valentina; Del Busto, Ramon; Limaye, Ajit P.; Somani, Jyoti; Lyon, Marshall; Houston, Sally; House, Andrew A.; Pruett, Timothy L.; Orloff, Susan; Humar, Atul; Dowdy, Lorraine; Garcia-Diaz, Julia; Kalil, Andre C; Fisher, Robert A.; Husain, Shahid.

In: Clinical Infectious Diseases, Vol. 40, No. 12, 15.06.2005, p. 1756-1761.

Research output: Contribution to journalArticle

Singh, N, Lortholary, O, Alexander, BD, Gupta, KL, John, GT, Pursell, K, Munoz, P, Klintmalm, GB, Stosor, V, Del Busto, R, Limaye, AP, Somani, J, Lyon, M, Houston, S, House, AA, Pruett, TL, Orloff, S, Humar, A, Dowdy, L, Garcia-Diaz, J, Kalil, AC, Fisher, RA & Husain, S 2005, 'An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients', Clinical Infectious Diseases, vol. 40, no. 12, pp. 1756-1761. https://doi.org/10.1086/430606
Singh, Nina ; Lortholary, Olivier ; Alexander, Barbara D. ; Gupta, Krishan L. ; John, George T. ; Pursell, Kenneth ; Munoz, Patricia ; Klintmalm, Goran B. ; Stosor, Valentina ; Del Busto, Ramon ; Limaye, Ajit P. ; Somani, Jyoti ; Lyon, Marshall ; Houston, Sally ; House, Andrew A. ; Pruett, Timothy L. ; Orloff, Susan ; Humar, Atul ; Dowdy, Lorraine ; Garcia-Diaz, Julia ; Kalil, Andre C ; Fisher, Robert A. ; Husain, Shahid. / An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients. In: Clinical Infectious Diseases. 2005 ; Vol. 40, No. 12. pp. 1756-1761.
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abstract = "Background. We describe an immune reconstitution syndrome (IRS)-like entity in the course of evolution of Cryptococcus neoformans infection in organ transplant recipients. Methods. The study population comprised a cohort of 83 consecutive organ transplant recipients with cryptococcosis who were observed for a median of 2 years in an international, multicenter study. Results. In 4 (4.8{\%}) of the 83 patients, an IRS-like entity was observed a median of 5.5 weeks after the initiation of appropriate antifungal therapy. Worsening of clinical manifestations was documented, despite cultures being negative for C. neoformans. These patients were significantly more likely to have received tacrolimus, mycophenolate mofetil, and prednisone as the regimen of immunosuppressive therapy than were all other patients (P = .007). The proposed basis of this phenomenon is reversal of a predominantly Th2 response at the onset of infection to a Th1 proinflammatory response as a result of receipt of effective antifungal therapy and a reduction in or cessation of immunosuppressive therapy. Conclusions. This study demonstrated that an IRS-like entity occurs in organ transplant recipients with C. neoformans infection. Furthermore, this entity may be misconstrued as a failure of therapy. Immunomodulatory agents may have a role as adjunctive therapy in such cases.",
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AU - Pursell, Kenneth

AU - Munoz, Patricia

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N2 - Background. We describe an immune reconstitution syndrome (IRS)-like entity in the course of evolution of Cryptococcus neoformans infection in organ transplant recipients. Methods. The study population comprised a cohort of 83 consecutive organ transplant recipients with cryptococcosis who were observed for a median of 2 years in an international, multicenter study. Results. In 4 (4.8%) of the 83 patients, an IRS-like entity was observed a median of 5.5 weeks after the initiation of appropriate antifungal therapy. Worsening of clinical manifestations was documented, despite cultures being negative for C. neoformans. These patients were significantly more likely to have received tacrolimus, mycophenolate mofetil, and prednisone as the regimen of immunosuppressive therapy than were all other patients (P = .007). The proposed basis of this phenomenon is reversal of a predominantly Th2 response at the onset of infection to a Th1 proinflammatory response as a result of receipt of effective antifungal therapy and a reduction in or cessation of immunosuppressive therapy. Conclusions. This study demonstrated that an IRS-like entity occurs in organ transplant recipients with C. neoformans infection. Furthermore, this entity may be misconstrued as a failure of therapy. Immunomodulatory agents may have a role as adjunctive therapy in such cases.

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