Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P < .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of cirrhotic patients with advanced liver disease cryptococcosis was first recognized after death. These patients had the characteristics of presenting with fulminant fungemia, were less likely to have positive serum cryptococcal antigen and posed a diagnostic challenge for care providers.

This chapter describes the epidemiology, clinical presentation, diagnosis, and management of infections caused by a diverse group of bacterial pathogens. These include classic opportunistic infections, such as listeriosis or nocardiosis, and also infections that are common in immunocompetent patients but particularly prevalent or morbid in transplant populations, such as Legionella pneumonia and Clostridium difficile infection. Some uncommon bacterial pathogens that have a predilection for patients with impaired immunity such as Mycoplasma hominis and Rhodococcus equi are also discussed. Finally, the chapter touches on some miscellaneous bacterial infections that are important because they may be unanticipated in transplant recipients or present diagnostic or therapeutic challenges.

BACKGROUND:The outcomes and optimal management of cirrhotic patients who develop cryptococcosis before transplantation are not fully known.METHODS:We conducted a multicenter study involving consecutive patients with cirrhosis and cryptococcosis between January 2000 and March 2014. Data collected were generated as standard of care.RESULTS:In all, 112 patients were followed until death or up to 9 years. Disseminated disease and fungemia were present in 76.8% (86/112) and 90-day mortality was 57.1% (64/112). Of the 39 patients listed for transplant, 20.5% (8) underwent liver transplantation, including 2 with active but unrecognized disease before transplantation. Median duration of pretransplant antifungal therapy and posttransplant therapy was 43 days (interquartile range, 8-130 days) and 272 days (interquartile range, 180-630 days), respectively. Transplantation was associated with lower mortality (P = 0.002). None of the transplant recipients developed disease progression during the median follow-up of 3.5 years with a survival rate of 87.5%.CONCLUSIONS:Cryptococcosis in patients with cirrhosis has grave prognosis. Our findings suggest that transplantation after recent cryptococcal disease may not be a categorical exclusion and may be cautiously undertaken in liver transplant candidates who are otherwise deemed clinically stable.

pro-interleukin-1b is cytosolic and precedes cell death. J Cell Sci 2007;120:772–81. 44. Ferrari D, Chiozzi P, Falzoni S, Dal Susino M, Melchiorri L, Baricordi OR, et al. Extracellular ATP triggers IL-1b release by activating the purinergic P2Z receptor of human macrophages. J Immunol 1997;159:1451–8. 45. Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL, et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 2008;9:847–56. 46. Baroja-Mazo A, Martin-Sanchez F, Gomez AI, Martinez CM, Amores-Iniesta J, Compan V, et al. The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response. Nat Immunol 2014;15:738–48. 47. Brydges SD, Broderick L, McGeough MD, Pena CA, Mueller JL, Hoffman HM. Divergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies. J Clin Invest 2013;123:4695–705.

Background. Histoplasmosis causes severe disease in patients with defects of cell-mediated immunity. It is not known whether outcomes vary related to the type of immunodeficiency or class of antifungal treatment. Methods. We reviewed cases of active histoplasmosis that occurred at Vanderbilt University Medical Center from July 1999 to June 2012 in patients with human immunodeficiency virus (HIV) infection, a history of transplantation, or tumor necrosis factor (TNF)-α inhibitor use. These groups were compared for differences in clinical presentation and outcomes. In addition, outcomes were related to the initial choice of treatment. Results. Ninety cases were identified (56 HIV, 23 transplant, 11 TNF-α inhibitor). Tumor necrosis factor-α patients had milder disease, shorter courses of therapy, and fewer relapses than HIV patients. Histoplasma antigenuria was highly prevalent in all groups (HIV 88%, transplant 95%, TNF-α 91%). Organ transplant recipients received amphotericin B formulation as initial therapy less often than other groups (22% vs 57% HIV vs 55% TNF-α; P = .006). Treatment failures only occurred in patients with severe disease. The failure rate was similar whether patients received initial amphotericin or triazole therapy. Ninety-day histoplasmosis-related mortality was 9% for all groups and did not vary significantly with choice of initial treatment. Conclusions. Histoplasmosis caused milder disease in patients receiving TNF-α inhibitors than patients with HIV or solid organ transplantation. Treatment failures and mortality only occurred in patients with severe disease and did not vary based on type of immunosuppression or choice of initial therapy.

Successful clinical organ transplantation dates from 1954, when the immunologic barrier to transplantation was ingeniously circumvented in a few patients with kidney failure by using organs from donors who were identical twins with the patients. Subsequently, transplantation of organs from genetically different individuals was attempted with lymphoid irradiation to suppress the recipient’s immune response to the allograft, but these efforts met with only occasional success. In the early 1960s, immunosuppressive regimens employing azathioprine and corticosteroids were introduced. These provided more effective control of allograft rejection that not only was sustainable but could be adjusted according to an individual patient’s circumstances. This development catapulted kidney transplantation beyond the experimental stage, and both living-related and cadaveric renal transplantation became part of regular clinical practice. Attempts at heart and liver transplantation proved more challenging, and these clinical efforts remained limited to a few dedicated programs for more than a decade. The next major watershed in the development of transplantation was the introduction of cyclosporine in the early 1980s. This development ushered in a marked expansion of heart and liver transplantation, promoted further growth of renal transplantation, and made lung transplantation possible. Currently, more than 28,000 solid organ transplantations are performed yearly in the United States, and most patients retain the grafts and survive many years after transplantation. As a result, patients with various types of transplants are now routinely encountered in general practice. Except for issues related to the function and rejection of the transplanted organ, infections are the most important problem after transplantation. The clinical manifestations of infection are variable and depend on the infecting pathogen, the prior immune status of the host, the type of transplantation, the time after transplantation, and the level of pharmacologic immunosuppression. With this complexity in mind, it is useful to address some general principles that may aid in the diagnosis, management, and understanding of infections after transplantation. The occurrence of infection requires a susceptible host and an available pathogen. Transplant recipients are not equally susceptible to all pathogens. For instance, most enteroviruses do not appear to infect transplant recipients with greater frequency or severity than they do normal hosts. A transplant recipient also may be quite susceptible to a given pathogen but may have a low risk of infection because of lack of exposure. For example, tuberculosis is rarely encountered at most transplantation centers in developed countries, but it can be a major problem in transplant recipients in parts of the world and in clinical settings in which infection cannot be avoided. Likewise, transplant recipients with no past exposure to cytomegalovirus (CMV) who receive organs from CMV-seronegative donors are at low risk for CMV infection, whatever their level of immunosuppression. In clinical practice, the clinician can and should use this sort of information to assess each patient’s individual susceptibility to important pathogens. Infections are most frequent and most varied during the first 6 months after transplantation. During this period, patients have all the risk factors for infection (Table 310-1): They may still be affected— either directly or indirectly—by their underlying disease; because they have undergone major surgery and been in the intensive care unit, they are at risk for wound and other nosocomial infections; and because they have received large doses of immunosuppressive drugs, the allograft may be malfunctioning as a result of rejection or other factors. This early period also covers the time of highest risk for infection by opportunistic microorganisms such as CMV and Nocardia, Aspergillus, Pneumocystis, or Toxoplasma organisms. These pathogens received much attention in the early literature on transplantation-related infections; more recently, their clinical impact has been diminished by the widespread use of antimicrobial prophylactic regimens early after transplantation. These regimens have virtually eliminated some infectious complications, such as Pneumocystis pneumonia, and have provided substantial but still imperfect control of others, such as CMV disease. With time—usually about 6 to 9 months after transplantation—the risk of infection tends to decrease. The level of vigilance may therefore be reduced, except for individual patients whose risk has remained high because of continued requirement for high doses of immunosuppression.

Background. Polyomavirus infection causes nephropathy after kidney transplantation but has not been thoroughly investigated in nonrenal organ transplantation.Methods. Ninety lung transplant recipients were enrolled, and they provided urine samples for over 4.5 years. Samples were analyzed for BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40) by conventional and quantitative real-time polymerase chain reaction.Results. Fifty-nine (66%) patients had polyomavirus detected at least once, including 38 patients (42%) for BKV, 25 patients (28%) for JCV, and six patients (7%) for SV40. Frequency of virus shedding in serial urine samples by patients positive at least once varied significantly among viruses: JCV, 64%; BKV, 48%; and SV40, 14%. Urinary viral loads for BKV (10(5.4) copies/mL) and JCV (10(6.0) copies/mL) were higher than for SV40 (10(2.5) copies/mL; P=0.001 and 0.0003, respectively). Polyomavirus infection was associated with a pretransplant diagnosis of chronic obstructive pulmonary disease (odds ratio 6.0; P=0.016) but was less common in patients with a history of acute rejection (odds ratio 0.28; P=0.016). SV40 infection was associated with sirolimus-based immunosuppression (P=0.037). Reduced survival was noted for patients with BKV infection (P=0.03). Patients with polyomavirus infection did not have worse renal function than those without infection, but in patients with BKV infection, creatinine clearances were lower at times when viral shedding was detected (P=0.038).Conclusions. BKV and JCV were commonly detected in the urine of lung transplant recipients; SV40 was found at low frequency. No definite impact of polyomavirus infection on renal function was documented. BKV infection was associated with poorer survival.

BACKGROUND:Information is limited on long-term outcomes after preemptive use of ganciclovir to control cytomegalovirus (CMV) infection in lung transplantation.METHODS:We studied 78 lung recipients who received antithymocyte globulin induction from 1994 to 2000. All patients received six months of oral acyclovir (800 mg TID). This was interrupted three wk post transplantation for a two-wk course of IV ganciclovir. Additional courses of ganciclovir were administered based on serial virological monitoring. CMV-mismatched patients (R-D+) also received four doses of CMV immunoglobulin between weeks 2 and 8.RESULTS:The one yr cumulative risk of CMV disease was 2% (1/61) in CMV seropositive (R+) patients, but was 37% (6/17) in R-D+ patients (p < 0.0001). Over 4.3 yr of follow-up, patients with CMV infection developed more chronic graft dysfunction caused by bronchiolitis obliterans or bronchiolitis obliterans syndrome than patients without CMV infection (p = 0.012). This effect was also apparent in the subgroup of R+ recipients (p = 0.043). Acute rejection and overall survival were not associated with CMV infection.CONCLUSIONS:The use of prophylactic acyclovir and short preemptive courses of ganciclovir effectively controlled CMV disease in R+ patients, but was a relative failure in R-D+ patients. CMV infection was significantly associated with chronic graft dysfunction, even in R+ recipients who had good control of CMV symptoms.

To characterize the impact of immunosuppression on human ehrlichiosis, we reviewed cases of ehrlichiosis occurring in transplant recipients and immunocompetent patients at three hospitals in Nashville, Tennessee. Between 1998 and 2006, 15 transplant patients were identified as having ehrlichiosis, diagnosed either by whole blood polymerase chain reaction (PCR) (n = 14) or serology (n = 1). They were compared with 43 immunocompetent patients diagnosed by whole blood PCR. We retrospectively collected demographic and clinical information. The species of Ehrlichia (E. ewingii or E. chaffeensis) was determined for patients diagnosed by PCR. The 15 transplant recipients with ehrlichiosis included 7 kidney recipients, 6 heart recipients, 1 liver recipient and 1 lung recipient. Transplant recipients had more infections with E. ewingii than immunocompetent patients (23% vs. 5%, p = 0.08). Transplant recipients experienced less rash (0% vs. 36%, p = 0.006) and presented with significantly lower hepatic enzymes, but more leukopenia and renal dysfunction than immunocompetent patients. Doxycycline therapy was started within 48 h of presentation in 73% of transplant recipients and 78% of immunocompetent patients (p = 0.7). No patient died in either group. Ehrlichia infections can occur in transplant recipients who live in an endemic area. With prompt treatment, the infected transplant recipients in our study had similar, favorable outcomes compared to immunocompetent patients.

The frequency and complications of respiratory viral infections (RVI) were studied in 50 ambulatory lung transplant patients during a single winter season, using viral antigens, viral cultures and PCR of nasal washes or bronchoalveolar lavages. Patients' survival, episodes of acute rejection and occurrence of bronchiolitis obliterans (BO) or BO syndrome (BOS) were monitored for 1 yr after the study.Overall, 32 (64%) patients had 49 symptomatic episodes. Documented infections included eight due to respiratory syncytial virus (RSV), one due to parainfluenza virus (PIV) and 10 due to influenza (FLU). Four of the FLU infections were serological rises without symptoms. Overall, 17 (34%) patients had documented viral infection; four patients had lower respiratory involvement and two (one RSV, one PIV) were hospitalised for aerosolised ribavirin treatment.After 1 yr there were three (6%) deaths unrelated to RVI. BO or BOS had occurred in one (6%) out of 17 patients with and three (12%) out of 33 without RVI. Respiratory viruses infected one-third of ambulatory lung transplant recipients in a single season.In conclusion, respiratory viral infection was not associated with subsequent graft dysfunction. Larger prospective studies are required to better define the acute and long-term morbidity of these infections.

Two patients who had undergone nonmyeloablative allogeneic stem cell transplantation 53 and 112 days earlier and were being monitored at the same transplant center developed severe Bordetella bronchiseptica infections within 3 days of each other. Pulsed-field gel electrophoresis analysis indicated that the isolates from the two cases were identical. Neither patient had had direct contact with animals since transplantation. These findings strongly support nosocomial transmission of B. bronchiseptica.

Cytomegalovirus encephalitis occurs rarely in transplant recipients. We describe a patient with cytomegalovirus ventriculoencephalitis who had a very high CSF viral load but a low peripheral blood viral load. No resistance mutations were present in cerebrospinal fluid viral DNA, whereas DNA from blood showed a resistance mutation in the UL54 gene but not in the UL97 gene. Viral replication was intense in the brain ependyma and periventricular areas without evidence of peripheral cytomegalovirus disease. The data provide evidence for compartmentalization of cytomegalovirus infection. Levels of ganciclovir and foscarnet in the cerebrospinal fluid may be inadequate for treatment, even for some drug-susceptible strains, and, together with periventricular replication, may explain the disparity between cerebrospinal fluid viral load and peripheral blood viral load.

Severe sepsis in lung transplant recipients is a challenging problem and carries a high mortality. Recombinant human activated protein C (drotrecogin alfa [activated]) has been approved for use in patients with severe sepsis. Its use has been shown to be safe and impart a survival advantage. However, the safety of drotrecogin alfa activated has not been evaluated in lung transplant recipients. We report for the first time on the use of drotrecogin alfa activated in six lung transplant recipients. Clinical trials are warranted to further evaluate the use of drotrecogin alfa activated in transplant recipients.

Editorials20 December 2005Controlling the Troll: Management of Cytomegalovirus Infection after TransplantationStephen Dummer, MDStephen Dummer, MDFrom Vanderbilt University Medical Center, Nashville, TN 37232.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-12-200512200-00010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Twenty-five years ago, Henry Balfour coined the phrase “troll of transplantation” to denote the insidious influence that cytomegalovirus (CMV) infection exerted on the outcome of transplantation (1). At that time, CMV was the most common serious pathogen in transplant recipients. Like the troll in the fairy tale, the virus was a hidden threat, latent in the recipient's or donor's tissues but ready to emerge under the pressure of immunosuppression. Although some patients only experienced subclinical CMV infection, other patients progressed to having overt CMV disease. These patients were readmitted to the hospital 1 to 2 months after transplantation and suffered ...References1. Balfour HH. Cytomegalovirus: the “transplant troll” takes its toll. Clin Microbiology Newsletter. 1980;2:1-3. CrossrefMedlineGoogle Scholar2. Cytomegalovirus. Am J Transplant. 2004;4 Suppl 10 51-8. [PMID: 15504213] CrossrefMedlineGoogle Scholar3. Preiksaitis JK, Brennan DC, Fishman J, Allen U. Canadian society of transplantation consensus workshop on cytomegalovirus management in solid organ transplantation final report. Am J Transplant. 2005;5:218-27. [PMID: 15643981] CrossrefMedlineGoogle Scholar4. Boeckh M, Boivin G. Quantitation of cytomegalovirus: methodologic aspects and clinical applications. Clin Microbiol Rev. 1998;11:533-54. [PMID: 9665982] CrossrefMedlineGoogle Scholar5. Cope AV, Sabin C, Burroughs A, Rolles K, Griffiths PD, Emery VC. Interrelationships among quantity of human cytomegalovirus (HCMV) DNA in blood, donor-recipient serostatus, and administration of methylprednisolone as risk factors for HCMV disease following liver transplantation. J Infect Dis. 1997;176:1484-90. [PMID: 9395358] CrossrefMedlineGoogle Scholar6. Kusne S, Grossi P, Irish W, St George K, Rinaldo C, Rakela J, et al. Cytomegalovirus PP65 antigenemia monitoring as a guide for preemptive therapy: a cost effective strategy for prevention of cytomegalovirus disease in adult liver transplant recipients. Transplantation. 1999;68:1125-31. [PMID: 10551640] CrossrefMedlineGoogle Scholar7. Snydman DR. Counterpoint: prevention of cytomegalovirus (CMV) infection and CMV disease in recipients of solid organ transplants: the case for prophylaxis. Clin Infect Dis. 2005;40:705-12. [PMID: 15714417] CrossrefMedlineGoogle Scholar8. Paya C, Humar A, Dominguez E, Washburn K, Blumberg E, Alexander B, et al. Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2004;4:611-20. [PMID: 15023154] CrossrefMedlineGoogle Scholar9. Lowance D, Neumayer HH, Legendre CM, Squifflet JP, Kovarik J, Brennan PJ, et al. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. N Engl J Med. 1999;340:1462-70. [PMID: 10320384] CrossrefMedlineGoogle Scholar10. Singh N. Preemptive therapy versus universal prophylaxis with ganciclovir for cytomegalovirus in solid organ transplant recipients. Clin Infect Dis. 2001;32:742-51. [PMID: 11229841] CrossrefMedlineGoogle Scholar11. Kalil AC, Levitsky J, Lyden E, Stoner J, Freifeld AG. Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med. 2005;143:870-80. LinkGoogle Scholar12. Fishman JA, Rubin RH. Infection in organ-transplant recipients. N Engl J Med. 1998;338:1741-51. [PMID: 9624195] CrossrefMedlineGoogle Scholar13. Wagner JA, Ross H, Hunt S, Gamberg P, Valantine H, Merigan TC, et al. Prophylactic ganciclovir treatment reduces fungal as well as cytomegalovirus infections after heart transplantation. Transplantation. 1995;60:1473-7. [PMID: 8545877] CrossrefMedlineGoogle Scholar14. Munoz-Price LS, Slifkin M, Ruthazer R, Poutsiaka DD, Hadley S, Freeman R, et al. The clinical impact of ganciclovir prophylaxis on the occurrence of bacteremia in orthotopic liver transplant recipients. Clin Infect Dis. 2004;39:1293-9. [PMID: 15494905] CrossrefMedlineGoogle Scholar15. Humar A, Kumar D, Preiksaitis J, Boivin G, Siegal D, Fenton J, et al. A trial of valganciclovir prophylaxis for cytomegalovirus prevention in lung transplant recipients. Am J Transplant. 2005;5:1462-8. [PMID: 15888055] CrossrefMedlineGoogle Scholar16. Singh N. Late-onset cytomegalovirus disease as a significant complication in solid organ transplant recipients receiving antiviral prophylaxis: a call to heed the mounting evidence. Clin Infect Dis. 2005;40:704-8. [PMID: 15714416] CrossrefMedlineGoogle Scholar17. Reusser P, Cathomas G, Attenhofer R, Tamm M, Thiel G. Cytomegalovirus (CMV)-specific T cell immunity after renal transplantation mediates protection from CMV disease by limiting the systemic virus load. J Infect Dis. 1999;180:247-53. [PMID: 10395836] CrossrefMedlineGoogle Scholar18. Li CR, Greenberg PD, Gilbert MJ, Goodrich JM, Riddell SR. Recovery of HLA-restricted cytomegalovirus (CMV)-specific T-cell responses after allogeneic bone marrow transplant: correlation with CMV disease and effect of ganciclovir prophylaxis. Blood. 1994;83:1971-9. [PMID: 8142663] CrossrefMedlineGoogle Scholar19. Singh N, Wannstedt C, Keyes L, Wagener MM, Gayowski T, Cacciarelli TV. Indirect outcomes associated with cytomegalovirus (opportunistic infections, hepatitis C virus sequelae, and mortality) in liver-transplant recipients with the use of preemptive therapy for 13 years. Transplantation. 2005;79:1428-34. [PMID: 15912115] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Stephen Dummer, MDAffiliations: From Vanderbilt University Medical Center, Nashville, TN 37232.Disclosures: Consultancies: Roche Labs; Honoraria: Roche Labs.Corresponding Author: Stephen Dummer, MD, Vanderbilt University Medical Center, 911 Oxford House, Nashville, TN 37232; e-mail, Stephen.[email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMeta-Analysis: The Efficacy of Strategies To Prevent Organ Disease by Cytomegalovirus in Solid Organ Transplant Recipients Andre C. Kalil , Josh Levitsky , Elizabeth Lyden , Julie Stoner , and Alison G. Freifeld Controlling the Troll Andre C. Kalil , Elizabeth Lyden , and Julie Stoner Controlling the Troll Stephen Dummer Metrics Cited byUtility of Leflunomide in the Treatment of Complex Cytomegalovirus SyndromesThe use of consensus guidelines for management of cytomegalovirus infection in renal transplantationCytomegalovirus-associated allograft rejection in heart transplant patientsControlling the TrollAndre C. Kalil, MD, Elizabeth Lyden, MS, and Julie Stoner, PhD 20 December 2005Volume 143, Issue 12Page: 913-914KeywordsAntiviral therapyAntiviralsCytomegalovirus infectionDrug therapyDrugsInfectious diseasesOral administrationProphylaxisTransplantationViral diseases ePublished: 20 December 2005 Issue Published: 20 December 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Coccidioidomycosis is endemic in the southwest United States, and impaired cellular immunity profoundly increases the susceptibility to life-threatening Coccidioides immitis infections. This study combines the clinical presentation of coccidioidomycosis in 5 renal transplant recipients in El Paso from 1987 to 2002 with details from 28 other cases published in the literature from 1966 to 2002. The 5 cases in El Paso occurred in a population of 297 transplant recipients. Overall, the 33 renal transplant recipients with coccidioidomycosis included 24 men and 9 women with a median age of 38 years. Fifty-eight percent of the patients were white, 33% Hispanic, 3% African American, 3% Native American, and 3% Asian. Twenty-three (70%) of the patients had cadaveric donors, and the remainder had living donors. Underlying renal diseases included chronic glomerulonephritis (48%), diabetes mellitus (30%), autoimmune diseases (3%), Alport syndrome (3%), and others not documented (16%). C. immitis was isolated from the lung in 75% of the patients; in the remaining 25%, it involved the spleen, urine, skin, pancreas, bone marrow, thyroid, choroid, and lymph nodes. In the majority of the patients, the initial clinical presentation included fever with clinical and radiographic evidence of pneumonia. The median time between transplantation and the diagnosis of infection was 6 months (15 days to 50 months). Disseminated coccidioidomycosis occurred in 18 patients. Treatment modalities included amphotericin B in 29 patients (88%) and fluconazole in 6 patients (18%). Death occurred in 55% (18) of the patients with 9 of them dying from coccidioidomycosis and the other 9 dying of other causes. There did not appear to be a significant increase in the mortality in patients who had underlying diabetes mellitus.

Background. Between 1955 and 1963, millions of individuals worldwide received vaccines contaminated with polyomavirus simian virus (SV)40. Recent data suggest that some individuals may develop renal dysfunction related to SV40 infection, including individuals too young to have received contaminated vaccines.Case Report and Results. Three years after bilateral lung transplantation, a 32-year-old man with cystic fibrosis developed nephrotic syndrome and progressed to end-stage renal failure over 1.5 years. He was shown to have nephropathy caused by SV40. The diagnosis was documented by detecting and confirming sequences of SV40 (but not BK or JC virus) in his kidney biopsy and urine by polymerase chain reaction, Southern blot, and DNA sequencing. Positive immunohistochemistry for SV40 was found in his kidney, and neutralizing antibodies for SV40 were detected in his serum, before and after the onset of renal dysfunction. A source for the virus was not determined. His household contacts did not have serologic or molecular evidence of SV40 infection. No serum or tissue samples were available from his 27-year-old donor.Discussion. This report shows that SV40 is circulating in the community and can cause nephropathy in transplant patients.