Aruna Subramanian

All Publications

• Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis. JCI insight Wilson, J. G., Simpson, L. J., Ferreira, A., Rustagi, A., Roque, J. A., Asuni, A., Ranganath, T., Grant, P. M., Subramanian, A. K., Rosenberg-Hasson, Y., Maecker, H., Holmes, S., Levitt, J. E., Blish, C., Rogers, A. J. 2020

  Abstract

  BACKGROUND: Elevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare to those observed in critically ill patients with ARDS or sepsis due to other causes.METHODS: We used a luminex assay to determine expression of 76 cytokines from plasma of hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients. Our analysis focused on detecting statistical differences in levels of 6 cytokines associated with cytokine storm (IL-1b, IL-1RA, IL-6, IL-8, IL-18, and TNFalpha) between patients with moderate COVID-19, severe COVID-19, and ARDS or sepsis.RESULTS: 15 hospitalized COVID-19 patients, 9 of whom were critically ill, were compared to critically ill patients with ARDS (n = 12) or sepsis (n = 16). There were no statistically significant differences in baseline levels of IL-1b, IL-1RA, IL-6, IL-8, IL-18, and TNFalpha between patients with COVID-19 and critically ill controls with ARDS or sepsis.CONCLUSIONS: Levels of inflammatory cytokines were not higher in severe COVID-19 patients than in moderate COVID-19 or critically ill patients with ARDS or sepsis in this small cohort. Broad use of immunosuppressive therapies in ARDS has failed in numerous Phase 3 studies; use of these therapies in unselected patients with COVID-19 may be unwarranted.FUNDING: A.J.R.: Stanford ICU Biobank NHLBI K23 HL125663. C.A.B.: Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases #1016687; NIH/NIAID U19AI057229-16 (PI MM Davis); Stanford Maternal Child Health Research Institute; Chan Zuckerberg Biohub.

  View details for DOI 10.1172/jci.insight.140289

  View details for PubMedID 32706339

• A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nature medicine Wilk, A. J., Rustagi, A., Zhao, N. Q., Roque, J., Martinez-Colon, G. J., McKechnie, J. L., Ivison, G. T., Ranganath, T., Vergara, R., Hollis, T., Simpson, L. J., Grant, P., Subramanian, A., Rogers, A. J., Blish, C. A. 2020

  Abstract

  There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, which has infected more than three million people worldwide1. Approximately 20% of patients with COVID-19 develop severe disease and 5% of patients require intensive care2. Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines3,4 that may be produced by a subset of inflammatory monocytes5,6, lymphopenia7,8 and T cell exhaustion9,10. To elucidate pathways in peripheral immune cells that might lead to immunopathology or protective immunity in severe COVID-19, we applied single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from seven patients hospitalized for COVID-19, four of whom had acute respiratory distress syndrome, and six healthy controls. We identify reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene signature, HLA class II downregulation and a developing neutrophil population that appears closely related to plasmablasts appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, we found that peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines. Collectively, we provide a cell atlas of the peripheral immune response to severe COVID-19.

  View details for DOI 10.1038/s41591-020-0944-y

  View details for PubMedID 32514174

• Antibiotic Exposure and Risk for Hospital-Associated Clostridioides difficile Infection. Antimicrobial agents and chemotherapy Webb, B. J., Subramanian, A., Lopansri, B., Goodman, B., Jones, P. B., Ferraro, J., Stenehjem, E., Brown, S. M. 2020

  Abstract

  Background: Clostridioides difficile infection (CDI) is a healthcare-associated infection associated with significant morbidity and cost with highly variable risk across populations. More effective, risk-based prevention strategies are needed. Here we investigate risk factors for hospital-associated CDI in a large integrated health system.Methods: In a retrospective cohort of all adult admissions to 21 Intermountain Healthcare hospitals from 2006 to 2012, we identified all symptomatic (1) hospital-onset and (2) healthcare-facility-associated, community-onset CDI. We then evaluated the risk associated with antibiotic exposure, including specific agents, using multivariable logistic regression.Results: 2356 cases of CDI among 506,068 admissions were identified (incidence 46.6 per 10,000). Prior antibiotic use was the dominant risk factor - for every antibiotic day of therapy prior to the index admission, odds of subsequent CDI increased by 12.8% (95% CI 12.2-13.4%, p<0.0001). This was a much stronger association than was inpatient antibiotic exposure (OR 1.007 (95% CI 1.005-1.009, p<0.0001). Highest risk antibiotics included 2nd generation and later cephalosporins (especially oral), carbapenems, fluroquinolones, and clindamycin, while doxycycline and daptomycin were associated with lower CDI risk.Conclusions: Cumulative antibiotic exposure prior to admission is the greatest contributor to risk of subsequent CDI. Most classes of antibiotics carry some risk, which varies by drug and route. This information may be useful for antimicrobial stewardship efforts.

  View details for DOI 10.1128/AAC.02169-19

  View details for PubMedID 31964789

• A Multicenter, Longitudinal Cohort Study of Cryptococcosis in Human Immunodeficiency Virus-negative People in the United States CLINICAL INFECTIOUS DISEASES Marr, K. A., Sun, Y., Spec, A., Lu, N., Panackal, A., Bennett, J., Pappas, P., Ostrander, D., Datta, K., Zhang, S. X., Williamson, P. R., Lyons, J., Bhimraj, A., Trotman, R., Perfect, J., Lyon, G., Vazquez, J., Piwoz, J., Marr, K., Spindel, S., Wray, D., Garcia-Diaz, J., Strasfeld, L., Nolt, D., Subramanian, A., Schaenman, J., Taplitz, R., Miceli, M., Lee, S. A., Hong Nguyen, Pannaraj, P., Hashun, R., Limaye, A., Powderly, W., Cryptococcus Infection Network Coh 2020; 70 (2): 252–61

  Abstract

  Cryptococcosis is increasingly recognized in people without human immunodeficiency virus (HIV).A multicenter, prospective cohort study was performed in 25 US centers. Consenting patients were prospectively followed for ≤2 years. Neurological morbidities were assessed with longitudinal event depiction and functional scores (Montreal Cognitive Assessment [MoCA]). Risks of death were analyzed using Cox regression.One hundred forty-five subjects were enrolled. Most were male (95; 65.5%) and had immunosuppression (120; 82.8%), including solid organ transplant (SOT; 33.8%), autoimmunity (15.9%), and hematologic malignancies (11.7%). Disease involved the central nervous system (CNS) in 71 subjects (49%). Fever was uncommon, documented in 40 (27.8%) subjects, and absence was associated with diagnostic delay (mean: 48.2 vs 16.5 days; P = .007). Abnormal MoCA scores (<26) were predictive of CNS disease; low scores (<22) were associated with poor long-term cognition. Longitudinal event depiction demonstrated frequent complications in people with CNS disease; 25 subjects (35.2%) required >1 lumbar puncture and 8 (11.3%) required ventriculostomies. In multivariable models, older age (>60 years) was associated with higher risks of death (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.05-4.38; P = .036), and lower risks were noted with underlying hematologic malignancy (HR, 0.29; 95% CI, 0.09-0.98; P = .05) and prior SOT (HR, 0.153; 95% CI, 0.05-0.44; P = .001).Despite aggressive antifungal therapies, outcomes of CNS cryptococcosis in people without HIV are characterized by substantial long-term neurological sequelae. Studies are needed to understand mechanism(s) of cognitive decline and to enable better treatment algorithms.

  View details for DOI 10.1093/cid/ciz193

  View details for Web of Science ID 000506801400013

  View details for PubMedID 30855688

  View details for PubMedCentralID PMC6938979

• Characteristics and outcomes of coronavirus disease patients under nonsurge conditions, northern California, USA, March–April 2020 Emerging Infectious Diseases Ferguson, J., Rosser, J., Quintero, O., Scott, J., Subramanian, A., Gumma, M., Rogers, A., Kappagoda, S. 2020

  Abstract

  Limited data are available on the clinical presentation and outcomes of coronavirus disease (COVID-19) patients in the United States hospitalized under normal-caseload or nonsurge conditions. We retrospectively studied 72 consecutive adult patients hospitalized with COVID-19 in 2 hospitals in the San Francisco Bay area, California, USA, during March 13-April 11, 2020. The death rate for all hospitalized COVID-19 patients was 8.3%, and median length of hospitalization was 7.5 days. Of the 21 (29% of total) intensive care unit patients, 3 (14.3% died); median length of intensive care unit stay was 12 days. Of the 72 patients, 43 (59.7%) had underlying cardiovascular disease and 19 (26.4%) had underlying pulmonary disease. In this study, death rates were lower than those reported from regions of the United States experiencing a high volume of COVID-19 patients.

  View details for DOI 10.3201/eid2608.201776

• Infections Related to Biologics. Infectious disease clinics of North America Ho, D. Y., Subramanian, A. K. 2020; 34 (2): xiii-xvi

  View details for DOI 10.1016/j.idc.2020.04.001

  View details for PubMedID 32444015

• Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. The New England journal of medicine Goldman, J. D., Lye, D. C., Hui, D. S., Marks, K. M., Bruno, R., Montejano, R., Spinner, C. D., Galli, M., Ahn, M. Y., Nahass, R. G., Chen, Y. S., SenGupta, D., Hyland, R. H., Osinusi, A. O., Cao, H., Blair, C., Wei, X., Gaggar, A., Brainard, D. M., Towner, W. J., Muñoz, J., Mullane, K. M., Marty, F. M., Tashima, K. T., Diaz, G., Subramanian, A. 2020

  Abstract

  Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19).We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale.In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%).In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.).

  View details for DOI 10.1056/NEJMoa2015301

  View details for PubMedID 32459919

• Simultaneous Coccidioidomycosis and Phaeohyphomycosis in a Kidney Transplant Recipient: A Case Report and Literature Review. Transplant infectious disease : an official journal of the Transplantation Society Puing, A. G., Couture-Cossette, A., Wang, A. X., Zygourakis, C. C., Cheng, X., Stevens, B. A., Banaei, N., Novoa, R. A., Ho, D. Y., Subramanian, A. 2020: e13365

  Abstract

  Advances in solid organ transplantation have improved the survival of end-stage organ disease at the expense of an increased risk for opportunistic infections. Unusual clinical presentations and the possibility of concurrent infections make diagnosing invasive fungal infection (IFI) more difficult. Here we present a case of simultaneous vertebral infection caused by Coccidioides immitis-posadasii and subcutaneous phaeohyphomycosis due to Nigrograna mackinnonii in a kidney transplant recipient. The diagnosis of both infections required invasive procedures to obtain tissue and a high index of suspicion that more than one IFI could be present. A multidisciplinary team approach for the management of immunocompromised patients with suspected or diagnosed IFI is warranted.

  View details for DOI 10.1111/tid.13365

  View details for PubMedID 32533741

• Mycobacterium tuberculosis infections in solid organ transplantation: Guidelines from the infectious diseases community of practice of the American Society of Transplantation CLINICAL TRANSPLANTATION Subramanian, A. K., Theodoropoulos, N. M., Amer Soc Transplantation 2019; 33 (9)

  View details for DOI 10.1111/ctr.13513

  View details for Web of Science ID 000489762300026

• Impact of Pretransplant Donor BK Viruria in Kidney Transplant Recipients JOURNAL OF INFECTIOUS DISEASES Tan, S. K., Huang, C., Sahoo, M. K., Weber, J., Kurzer, J., Stedman, M. R., Concepcion, W., Gallo, A. E., Alonso, D., Srinivas, T., Storch, G. A., Subramanian, A. K., Tan, J. C., Pinsky, B. A. 2019; 220 (3): 370–76

  View details for DOI 10.1093/infdis/jiz114

  View details for Web of Science ID 000477595700005

• Association of Antibiotic Resistance With Antibiotic Use for Epidermal Growth Factor Receptor Inhibitor-Related Papulopustular Eruption JAMA DERMATOLOGY Hirotsu, K., Dang, T. M., Li, S., Neal, J. W., Pugliese, S., Subramanian, A., Kwong, B. Y. 2019; 155 (7): 848–50

  View details for DOI 10.1001/jamadermatol.2019.0063

  View details for Web of Science ID 000482127300016

• Successful eradication of chronic symptomatic Candida krusei urinary tract infection with increased dose micafungin in a liver and kidney transplant recipient: case report and review of the literature. Transplant infectious disease : an official journal of the Transplantation Society Multani, A., Subramanian, A. K., Liu, A. Y. 2019: e13118

  Abstract

  Treatment of symptomatic candiduria is notoriously challenging because of the limited repository of antifungals that achieve adequate urinary concentrations. Fluconazole, amphotericin B-based products, and flucytosine are established treatment options for most Candida species. Candida krusei exhibits intrinsic resistance to fluconazole and decreased susceptibility to amphotericin B and flucytosine. In transplant patients, both amphotericin B-based products and flucytosine are less desirable due to their toxicities. Other triazole antifungals are unappealing because they do not achieve adequate urinary concentrations, have multiple toxicities, and interact with transplant-related immunosuppressive medications. Echinocandins are well-tolerated but have been traditionally deferred in the treatment of symptomatic funguria because of their poor urinary concentrations but there is a small but emerging body of literature supporting their use. Here, we present a case of successful eradication of chronic symptomatic Candida krusei urinary tract infection with micafungin 150 milligrams daily in a liver and kidney transplant recipient, and we review the literature on treatment of symptomatic candiduria. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/tid.13118

  View details for PubMedID 31111613

• Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors AMERICAN JOURNAL OF TRANSPLANTATION Kwong, A. J., Wall, A., Melcher, M., Wang, U., Ahmed, A., Subramanian, A., Kwo, P. Y. 2019; 19 (5): 1380–87

  View details for DOI 10.1111/ajt.15162

  View details for Web of Science ID 000471342300016

• Impact of Pre-Transplant Donor BK Viruria in Kidney Transplant Recipients. The Journal of infectious diseases Tan, S. K., Huang, C., Sahoo, M. K., Weber, J., Kurzer, J., Stedman, M. R., Concepcion, W., Gallo, A. E., Alonso, D., Srinivas, T., Storch, G. A., Subramanian, A. K., Tan, J. C., Pinsky, B. A. 2019

  Abstract

  BACKGROUND: BK virus (BKV) is a significant cause of nephropathy in kidney transplantation. The goal of this study was to characterize the course and source of BKV in kidney transplant recipients.METHODS: We prospectively collected pre-transplant plasma and urine samples from living and deceased kidney donors and performed BKV PCR and IgG testing on pre-transplant and serially collected post-transplant samples in kidney transplant recipients.RESULTS: Among deceased donors, 8.1%(17/208) had detectable BKV DNA in urine prior to organ procurement. BK viruria was observed in 15.4%(6/39) of living donors and 8.5%(4/47) of deceased donors of recipients at our institution (p=0.50). BKV VP1 sequencing revealed identical virus between donor-recipient pairs to suggest donor transmission of virus. Recipients of BK viruric donors were more likely to develop BK viruria (66.6%vs.7.8%, p<0.001) and viremia (66.6%vs.8.9%, p<0.001) with a shorter time to onset (log-rank, p<0.001). Though donor BKV IgG titers were higher in recipients who developed BK viremia, pre-transplant donor, recipient, and combined donor/recipient serology status was not associated with BK viremia (p=0.31,0.75,0.51,respectively).DISCUSSION: Donor BK viruria is associated with early BK viruria and viremia in kidney transplant recipients. BKV PCR testing of donor urine may be useful in identifying recipients at-risk for BKV complications.

  View details for PubMedID 30869132

• Mycobacterium tuberculosis Infections in Solid Organ Transplantation: Guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation. Clinical transplantation Subramanian, A. K., Theodoropoulos, N. M., Infectious Diseases Community of Practice of the American Society of Transplantation 2019: e13513

  Abstract

  These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention and management of tuberculosis in the pre- and post-transplant period. The challenges of screening for both latent and active TB in the setting of transplantation are reviewed. The use of interferon gamma release assays for detection of latent tuberculosis is discussed and compared to tuberculin skin testing. Given the limitations of both testing modality, it is important to consider exposure history and chest imaging. The clinical manifestations of active tuberculosis in transplantation are covered. New recommendations for treatment of latent tuberculosis and active tuberculosis are included. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30817030

• Association of Antibiotic Resistance With Antibiotic Use for Epidermal Growth Factor Receptor Inhibitor-Related Papulopustular Eruption. JAMA dermatology Hirotsu, K., Dang, T. M., Li, S., Neal, J. W., Pugliese, S., Subramanian, A., Kwong, B. Y. 2019

  View details for PubMedID 31017625

• Incidence of Active Tuberculosis Following Hematopoietic Cell Transplantation: A Small but Real Threat. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Aronson, J. R., Rezvani, A. R., Subramanian, A. 2019

  View details for DOI 10.1093/cid/ciz592

  View details for PubMedID 31297538

• Use of Alternative Agents for Prevention of Opportunistic Infections in Heart and Lung Transplant Recipients CLINICAL INFECTIOUS DISEASES Epstein, D. J., Benamu, E., Subramanian, A. K. 2018; 67 (10): 1637–39

  View details for DOI 10.1093/cid/ciy397

  View details for Web of Science ID 000450051300025

• Liver Transplantation for HCV Non-Viremic Recipients with HCV Viremic Donors. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Kwong, A. J., Wall, A., Melcher, M., Wang, U., Ahmed, A., Subramanian, A., Kwo, P. Y. 2018

  Abstract

  In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing (NAT). Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non-viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12 weeks post-treatment (SVR-12) with DAA-based regimens, with a median time from transplant to treatment initiation of 43 days (IQR 20-59). There have been no instances of graft loss or death, with median follow-up of 380 days (IQR 263-434) post-transplant. Transplantation of HCV-viremic livers into non-viremic recipients results in acceptable short-term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30378723

• Native Kidney Cytomegalovirus Nephritis and Cytomegalovirus Prostatitis in a Kidney Transplant Recipient. Transplant infectious disease : an official journal of the Transplantation Society Tan, S. K., Cheng, X. S., Kao, C., Weber, J., Pinsky, B. A., Gill, H. S., Busque, S., Subramanian, A. K., Tan, J. C. 2018: e12998

  Abstract

  We present a case of cytomegalovirus (CMV) native kidney nephritis and prostatitis in a CMV D+/R- kidney transplant recipient who had completed six months of CMV prophylaxis four weeks prior to the diagnosis of genitourinary CMV disease. The patient had a history of benign prostatic hypertrophy and urinary retention that required self-catheterization to relieve high post-voiding residual volumes. At 7 months post-transplant, he was found to have a urinary tract infection, moderate hydronephrosis of the transplanted kidney, and severe hydroureteronephrosis of the native left kidney and ureter, and underwent native left nephrectomy and transurethral resection of the prostate. Histopathologic examination of kidney and prostate tissue revealed CMV inclusions consistent with invasive CMV disease. This case highlights that CMV may extend beyond the kidney allograft to involve other parts of the genitourinary tract, including the native kidneys and prostate. Furthermore, we highlight the tissue-specific risk factors that preceded CMV tissue invasion. In addition to concurrent diagnoses, health care providers should have a low threshold for considering late-onset CMV disease in high-risk solid organ transplant recipients presenting with signs and symptoms of genitourinary tract pathology. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30203504

• Tuberculosis Recommendations for Solid Organ Transplant Recipients and Donors TRANSPLANTATION Santoro-Lopes, G., Subramanian, A. K., Molina, I., Maria Aguado, J., Rabagliatti, R., Len, O. 2018; 102 (2): S60–S65

  View details for PubMedID 29381579

• Use of Alternative Agents for Prevention of Opportunistic Infections in Heart and Lung Transplant Recipients. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Epstein, D. J., Benamu, E., Subramanian, A. 2018

  View details for PubMedID 29771330

• Prevention and Management of Tuberculosis in Solid Organ Transplant Recipients. Infectious disease clinics of North America Epstein, D. J., Subramanian, A. K. 2018; 32 (3): 703–18

  Abstract

  Solid organ transplant recipients are at an increased risk of tuberculosis and transplant candidates should be screened early in their evaluation with a detailed history, tuberculin skin test or tuberculosis interferon-gamma release assay, and chest radiograph. For latent tuberculosis treatment, isoniazid and rifamycin-based regimens have advantages and disadvantages; treatment decisions should be customized. Tuberculosis after solid organ transplantation generally occurs after months or years; early infections should raise the possibility of donor-derived infections. Tuberculosis diagnosis and treatment in solid organ transplant recipients may be complicated by protean manifestations, drug interactions, and adverse drug reactions.

  View details for PubMedID 30146031

• False-positive QuantiFERON TB-Gold test due to Mycobacterium gordonae DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE Gajurel, K., Subramanian, A. K. 2016; 84 (4): 315-317

  Abstract

  We report a case of QuantiFERON TB-Gold conversion associated to Mycobacterium gordonae in an elderly male from an assisted living facility without known risk factors for tuberculosis. This knowledge of environmental mycobacteria causing positive quantiferon assays is important to avoid unnecessary treatment of false-positive latent tuberculosis, especially in the absence of well-established positive predictive value of quantiferon conversion.

  View details for DOI 10.1016/j.diagmicrobio.2015.10.020

  View details for Web of Science ID 000372768800008

• False-positive hepatitis C virus serology after placement of a ventricular assistance device TRANSPLANT INFECTIOUS DISEASE Durand, C. M., Marr, K. A., OSTRANDER, D., Subramanian, A., Valsamakis, A., Cox, A., Neofytos, D. 2016; 18 (1): 146-149

  Abstract

  Ventricular assist devices (VADs) have been associated with immune activation and sensitization. We observed several cases of false-positive (FP) hepatitis C virus (HCV) antibody (Ab) tests in patients being evaluated for orthotopic heart transplant (OHT), prompting us to investigate this further.We reviewed all VAD and OHT cases at Johns Hopkins from 2005 to 2012. FP HCV serology was defined as an equivocal or low-positive HCV Ab, plus either (i) a negative recombinant immunoblot (RIBA) and/or HCV nucleic acid test (NAT), or (ii) an indeterminate RIBA and negative NAT.In 53 patients with available HCV testing, nearly 40% of patients (21/53: 39.6%) developed FP HCV Ab tests after VAD placement: 4 patients had negative NAT, 12 had negative RIBA, and 5 had an indeterminate RIBA and negative NAT. All patients with indeterminate RIBA tests had isolated reactivity to the same HCV protein, c100p/5-1-1p (NS4b protein). In 3 of 4 VAD patients who had OHT and repeat HCV Ab testing after VAD removal, repeat HCV Ab was negative (699-947 days after OHT); in 1 case, FP HCV serology persisted (5 days after OHT). Thirteen patients had OHT alone and none developed a FP HCV Ab.FP HCV Ab results following VAD placement are very common. Reversal of FP serology in several patients after VAD removal is suggestive of a possible association with the VAD hardware. Clinicians should be aware of this phenomenon, as it could lead to delays in determining eligibility for OHT and increased costs.

  View details for DOI 10.1111/tid.12483

  View details for Web of Science ID 000370449800021

  View details for PubMedID 26565742

• Survival in HIV-positive transplant recipients compared with transplant candidates and with HIV-negative controls. AIDS (London, England) Roland, M. E., Barin, B., Huprikar, S., Murphy, B., Hanto, D. W., Blumberg, E., Olthoff, K., Simon, D., Hardy, W. D., Beatty, G., Stock, P. G. 2016; 30 (3): 435–44

  Abstract

  To evaluate the impact of liver and kidney transplantation on survival in HIV-positive transplant candidates and compare outcomes between HIV-positive and negative recipients.Observational cohort of HIV-positive transplant candidates and recipients and secondary analysis comparing study recipients to HIV-negative national registry controls.We fit proportional hazards models to assess transplantation impact on mortality among recipients and candidates. We compared time to graft failure and death with HIV-negative controls in unmatched, demographic-matched, and risk-adjusted models.There were 17 (11.3%) and 46 (36.8%) deaths among kidney and liver recipients during a median follow-up of 4.0 and 3.5 years, respectively. Transplantation was associated with survival benefit for HIV-infected liver recipients with model for end-stage liver disease (MELD) greater than or equal 15 [hazard ratio (HR) 0.1; 95% confidence interval (CI) 0.05, 0.01; P < 0.0001], but not for MELD less than 15 (HR 0.7; 95% CI 0.3, 1.8; P = 0.43) or for kidney recipients (HR 0.6; 95% CI 0.3, 1.4; P = 0.23). In HIV-positive kidney recipients, unmatched and risk-matched analyses indicated a marginally significant HR for graft loss [1.3 (P = 0.07) and HR 1.4 (P = 0.052)]; no significant increase in risk of death was observed. All models demonstrated a higher relative hazard of graft loss or death in HIV-positive liver recipients; the absolute difference in the proportion of deaths was 6.7% in the risk-matched analysis.Kidney transplantation should be standard of care for well managed HIV-positive patients. Liver transplant in candidates with high MELD confers survival benefit; transplant is a viable option in selected candidates. The increased mortality risk compared with HIV-negative recipients was modest.ClinicalTrials.Gov; NCT00074386; http://clinicaltrials.gov/.

  View details for DOI 10.1097/QAD.0000000000000934

  View details for PubMedID 26765937

  View details for PubMedCentralID PMC4957135

• Tolerability of Fluoroquinolones in Management of Latent Tuberculosis in Liver Transplant Candidates CLINICAL INFECTIOUS DISEASES Tien, V., Robilotti, E., Callister, D., Subramanian, A., Lutchman, G., Ho, D. Y. 2015; 61 (10): 1631–U154

  View details for PubMedID 26224000

• Tuberculosis in solid organ transplant candidates and recipients: current and future challenges. Current opinion in infectious diseases Subramanian, A. K. 2014; 27 (4): 316-321

  Abstract

  Tuberculosis (TB) infection in solid organ transplant recipients poses unique diagnostic and treatment challenges. Recent guidelines for prevention of donor-derived TB and updates on TB diagnostics and treatment in the transplant setting are reviewed as follows.Prevention of donor-derived TB can be optimized by careful screening of donors with risk factors for TB, with effort taken to rule out active TB in the donor, and targeted treatment of recipients. However, transmission may still occur, especially through lung allografts, given limitations of screening tests and treatment strategies. Diagnostics for latent tuberculosis infection are limited in sensitivity and have a relatively low predictive value for development of active TB. Treatment options for latent and active TB carry risks that are still being elucidated in transplant patients, such as a dysregulated inflammatory response manifested by immune reconstitution syndrome.More sensitive diagnostics in deceased donors are needed to quantify the risk of TB transmission and the risk of progression to active tuberculosis in those with latent tuberculosis infection prior to transplant. Novel TB therapies of shorter duration with less toxicity for both latent and active TB will be of great benefit to transplant patients.

  View details for DOI 10.1097/QCO.0000000000000082

  View details for PubMedID 24977684

• Epidemiology, risk factors, and outcomes of Clostridium difficile infection in kidney transplant recipients TRANSPLANT INFECTIOUS DISEASE Neofytos, D., Kobayashi, K., Alonso, C. D., Cady-Reh, J., Lepley, D., Harris, M., Desai, N., Kraus, E., Subramanian, A., TREADWAY, S., OSTRANDER, D., Thompson, C., Marr, K. 2013; 15 (2): 134-141

  Abstract

  We sought to describe the epidemiology and risk factors for Clostridium difficile infection (CDI) among kidney transplant recipients (KTR) between 1 January 2008 and 31 December 2010.A single-institution retrospective study was conducted among all adult KTR with CDI, defined as a positive test for C. difficile by a cell cytotoxic assay for C. difficile toxin A or B or polymerase chain reaction test for toxigenic C. difficile.Among 603 kidney transplants performed between 1 January 2008 and 31 December 2010, 37 (6.1%) patients developed CDI: 12 (of 128; 9.4%) high-risk (blood group incompatible and/or anti-human leukocyte antigen donor-specific antibodies) vs. 25 (of 475; 5.3%, P = 0.08) standard-risk patients. The overall rate of CDI increased from 3.7% in 2008 to 9.4% in 2010 (P = 0.05). The median time to CDI diagnosis was 9 days, with 27 (73.0%) patients developing CDI within the first 30 days after their transplant, and 14 (51.8%) developing CDI within 7 days. A case-control analysis of 37 CDI cases and 74 matched controls demonstrated the following predictors for CDI among KTR: vancomycin-resistant Enterococcus colonization before transplant (odds ratio [OR]: 3.6, P = 0.03), receipt of an organ from Centers for Disease Control high-risk donor (OR: 5.9, P = 0.006), and administration of high-risk antibiotics within 30 days post transplant (OR: 6.6, P = 0.001).CDI remains a common early complication in KTR, with rates steadily increasing during the study period. Host and transplant-related factors and exposure to antibiotics appeared to significantly impact the risk for CDI among KTR.

  View details for DOI 10.1111/tid.12030

  View details for Web of Science ID 000317287900011

  View details for PubMedID 23173772

• Mycobacterium tuberculosis Infections in Solid Organ Transplantation AMERICAN JOURNAL OF TRANSPLANTATION Subramanian, A. K., Morris, M. I. 2013; 13: 68-76

  View details for DOI 10.1111/ajt.12100

  View details for Web of Science ID 000315907900009

  View details for PubMedID 23465000

• Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection LIVER TRANSPLANTATION Terrault, N. A., Roland, M. E., Schiano, T., Dove, L., Wong, M. T., Poordad, F., Ragni, M. V., Barin, B., Simon, D., Olthoff, K. M., Johnson, L., Stosor, V., Jayaweera, D., Fung, J., Sherman, K. E., Subramanian, A., Millis, J. M., Slakey, D., Berg, C. L., Carlson, L., Ferrell, L., Stablein, D. M., Odim, J., Fox, L., Stock, P. G. 2012; 18 (6): 716-726

  Abstract

  Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.

  View details for DOI 10.1002/lt.23411

  View details for Web of Science ID 000304524000012

  View details for PubMedID 22328294

• Fungal infection presenting as giant cell tubulointerstitial nephritis in kidney allograft TRANSPLANT INFECTIOUS DISEASE Bagnasco, S. M., Subramanian, A. K., Desai, N. M. 2012; 14 (3): 288-291

  Abstract

  Giant cell tubulointerstitial nephritis in the kidney allograft caused by infection is rare, and donor-transmitted infection in transplanted kidneys is also rare. In this case report, we describe an unusual histological manifestation of Candida albicans in the graft biopsy of a 53-year-old male kidney transplant recipient with decreased renal function 12 days post transplant. Several giant cells were present in the tubulointerstitial inflammation, as well as yeasts, with no evidence of rejection, and the histological diagnosis was confirmed by urine culture. Donor urine culture was positive for C. albicans, suggestive of a possible donor-transmitted infection. Prompt antifungal treatment eradicated the infection, and averted systemic spread. To our knowledge, there are no previous reports of Candida infection with giant cell tubulointerstitial nephritis in human renal allograft.

  View details for DOI 10.1111/j.1399-3062.2011.00676.x

  View details for Web of Science ID 000305076700009

  View details for PubMedID 22093412

• Donor-derived organ transplant transmission of coccidioidomycosis TRANSPLANT INFECTIOUS DISEASE Dierberg, K. L., Marr, K. A., Subramanian, A., Nace, H., Desai, N., Locke, J. E., Zhang, S., Diaz, J., Chamberlain, C., Neofytos, D. 2012; 14 (3): 300-304

  Abstract

  Coccidioidomycosis in solid organ transplant recipients most often occurs as a result of primary infection or reactivation of latent infection. Herein, we report a series of cases of transplant-related transmission of coccidioidomycosis from a single donor from a non-endemic region whose organs were transplanted to 5 different recipients. In all, 3 of the 5 recipients developed evidence of Coccidioides infection, 2 of whom had disseminated disease. The degree of T-cell immunosuppression and timing of antifungal therapy initiation likely contributed to development of disease and disease severity in these recipients. This case series highlights the importance of having a high index of suspicion for Coccidioides infection in solid organ transplant recipients, even if the donor does not have known exposure, given the difficulties of obtaining a detailed and accurate travel history from next-of-kin.

  View details for DOI 10.1111/j.1399-3062.2011.00696.x

  View details for Web of Science ID 000305076700012

  View details for PubMedID 22176496

• Actinomucor elegans as an Emerging Cause of Mucormycosis JOURNAL OF CLINICAL MICROBIOLOGY Mahmud, A., Lee, R., Munfus-McCray, D., Kwiatkowski, N., Subramanian, A., Neofytos, D., Carroll, K., Zhang, S. X. 2012; 50 (3): 1092-1095

  Abstract

  We report an invasive mucormycosis caused by Actinomucor elegans in a patient with refractory aplastic anemia. The organism was isolated from a necrotic skin lesion on the patient's left arm and demonstrated angioinvasive features on histopathology examination. In contrast to three cases described previously, we describe the first case of A. elegans invasive fungal infection in an immunocompromised patient. This report, along with the three previously reported cases, is convincing evidence that A. elegans is an emerging fungal pathogen capable of causing invasive mucormycosis in humans.

  View details for DOI 10.1128/JCM.05338-11

  View details for Web of Science ID 000300997800090

  View details for PubMedID 22205785

  View details for PubMedCentralID PMC3295095

• Antimicrobial prophylaxis regimens following transplantation CURRENT OPINION IN INFECTIOUS DISEASES Subramanian, A. K. 2011; 24 (4): 344-349

  Abstract

  Infection remains a major cause of morbidity and mortality following transplantation, and antimicrobial prophylaxis regimens continue to improve. This review summarizes the important studies on prophylaxis following solid organ transplant (SOT) and hematopoietic stem cell transplantation (HSCT) published in the last 18 months.Many transplant centers use 100 days of antivirals to prevent cytomegalovirus (CMV) disease after SOT. Randomized trials comparing 100-day regimens to 200 days in high-risk kidney recipients and 12 months in lung transplant patients showed distinct advantages of longer duration CMV prophylaxis. Prevention of hepatitis B virus after transplant is changing as regimens with low dose or no hepatitis B immunoglobulin are being evaluated. International consensus guidelines on the prevention of infection after stem cell transplantation are summarized and newer studies on the prevention of invasive fungal infection in this population are reviewed.In organ transplantation, routine antibacterial, antiviral, and antifungal regimens need to be tailored to address donor-transmitted infections, serological risk status of recipients, and measurable antifungal drug levels. Recent studies indicate that longer duration prophylaxis for CMV may have advantages in high-risk SOT recipients. After HSCT, regimens require adjustment based on immunological risks associated with transplant type and presence of graft vs. host disease.

  View details for DOI 10.1097/QCO.0b013e328348b379

  View details for Web of Science ID 000292185700007

  View details for PubMedID 21673573

• Provider Response to a Rare but Highly Publicized Transmission of HIV Through Solid Organ Transplantation ARCHIVES OF SURGERY Kucirka, L. M., Ros, L., Subramanian, A. K., Montgomery, R. A., Segev, D. L. 2011; 146 (1): 41-45

  Abstract

  On November 13, 2007, the first reported case in 20 years of HIV (human immunodeficiency virus) transmission from a Centers for Disease Control and Prevention high-risk donor (HRD) made national headlines. We sought to characterize change in the practice of transplant surgeons resulting from this rare event.We performed a survey between January 17, 2008, and April 15, 2008, assessing attitudes and practices of transplant surgeons regarding HRDs. Descriptions of changes in practice after the event were categorized, and associations between responses and regional-, center-, and physician-level factors were studied.Transplant centers in the United States.Four hundred twenty-two transplant surgeons in current practice.Changing practice following the 2007 HIV transmission event.Among surgeons who responded to the survey, 31.6% changed their practice following the event. Also, 41.7% decreased use of HRDs, 34.5% increased emphasis on informed consent, 16.7% increased use of nucleic acid testing, and 6.0% implemented a formal policy. Ranking fear of being sued or hospital pressure as important disincentives to HRD use was associated with more than 2-fold higher odds of changing practice. Ranking medical risks of HIV as an important disincentive was associated with 8.29-fold higher odds of decreasing HRD use.The most common responses to this rare event were avoidance (decreased HRD use) and assurance (increased emphasis on informed consent) behaviors rather than patient safety measures (increased use of nucleic acid testing and implementation of formal policies), suggesting that fear of legal or regulatory consequences was the biggest driver of physician decision making and that the current litigious environment is failing to protect patient interests.

  View details for Web of Science ID 000286235500014

  View details for PubMedID 21242444

• Outcomes of Kidney Transplantation in HIV-Infected Recipients 9th American Transplant Congress Stock, P. G., Barin, B., Murphy, B., Hanto, D., Diego, J. M., Light, J., Davis, C., Blumberg, E., Simon, D., Subramanian, A., Millis, J. M., Lyon, G. M., Brayman, K., Slakey, D., Shapiro, R., Melancon, J., Jacobson, J. M., Stosor, V., Olson, J. L., Stablein, D. M., Roland, M. E. MASSACHUSETTS MEDICAL SOC. 2010: 2004–14

  Abstract

  The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood.We undertook a prospective, nonrandomized trial of kidney transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least 200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels while being treated with a stable antiretroviral regimen. Post-transplantation management was provided in accordance with study protocols that defined prophylaxis against opportunistic infection, indications for biopsy, and acceptable approaches to immunosuppression, management of rejection, and antiretroviral therapy.Between November 2003 and June 2009, a total of 150 patients underwent kidney transplantation; survivors were followed for a median period of 1.7 years. Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%. In general, these rates fall somewhere between those reported in the national database for older kidney-transplant recipients (≥65 years) and those reported for all kidney-transplant recipients. A multivariate proportional-hazards analysis showed that the risk of graft loss was increased among patients treated for rejection (hazard ratio, 2.8; 95% confidence interval [CI], 1.2 to 6.6; P=0.02) and those receiving antithymocyte globulin induction therapy (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P=0.03); living-donor transplants were protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.8; P=0.02). A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively. HIV infection remained well controlled, with stable CD4+ T-cell counts and few HIV-associated complications.In this cohort of carefully selected HIV-infected patients, both patient- and graft-survival rates were high at 1 and 3 years, with no increases in complications associated with HIV infection. The unexpectedly high rejection rates are of serious concern and indicate the need for better immunotherapy. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00074386.).

  View details for Web of Science ID 000284310000005

  View details for PubMedID 21083386

  View details for PubMedCentralID PMC3028983

• Infections in Transplant and Oncology Patients Preface INFECTIOUS DISEASE CLINICS OF NORTH AMERICA Marr, K. A., Subramanian, A. K. 2010; 24 (2): XIII-XV

  View details for PubMedID 20466268

• Recommended curriculum for subspecialty training in transplant infectious disease on behalf of the American Society of Transplantation Infectious Diseases Community of Practice Educational Initiatives Working Group TRANSPLANT INFECTIOUS DISEASE Avery, R., CLAUSS, H., Danziger-Isakov, L., Davis, J., Doucette, K., van Duin, D., FISHMAN, J., Gunseren, F., Humar, A., Husain, S., Isada, C., Julian, K., Kaul, D., Kumar, D., Martin, S., Michaels, M., Morris, M., SILVEIRA, F., Subramanian, A. 2010; 12 (3): 190-194

  Abstract

  The American Society of Transplantation Infectious Diseases (ID) Community of Practice has established an education workgroup to identify core components of a curriculum for training specialists in transplant ID. Clinical, laboratory, and research training form the triad of components on which an additional year of ID training, dedicated to the care of solid organ and hematopoietic stem cell transplant recipients, should be based. The recommended training environment would have access to adequate numbers of transplant patients, along with qualified faculty committed to teaching specialized fellows in this area. The learning objectives for both inpatient and outpatient clinical training are presented. The laboratory component requires trainees to attain expertize in utilizing and interpreting cutting-edge diagnostics used in transplant medicine. The research component may involve basic science, and translational or clinical research individualized to the trainee. Finally, suggestions for evaluation of both the fellows and the training program are provided.

  View details for DOI 10.1111/j.1399-3062.2010.00510.x

  View details for Web of Science ID 000278315600002

  View details for PubMedID 20624259

• MELD Score Is an Important Predictor of Pretransplantation Mortality in HIV-Infected Liver Transplant Candidates GASTROENTEROLOGY Subramanian, A., Sulkowski, M., Barin, B., Stablein, D., Curry, M., Nissen, N., Dove, L., Roland, M., Florman, S., Blumberg, E., Stosor, V., Jayaweera, D. T., Huprikar, S., Fung, J., Pruett, T., Stock, P., Ragni, M. 2010; 138 (1): 159-164

  Abstract

  Human immunodeficiency virus (HIV) infection accelerates liver disease progression in patients with hepatitis C virus (HCV) and could shorten survival of those awaiting liver transplants. The Model for End-Stage Liver Disease (MELD) score predicts mortality in HIV-negative transplant candidates, but its reliability has not been established in HIV-positive candidates.We evaluated predictors of pretransplantation mortality in HIV-positive liver transplant candidates enrolled in the Solid Organ Transplantation in HIV: Multi-Site Study (HIVTR) matched 1:5 by age, sex, race, and HCV infection with HIV-negative controls from the United Network for Organ Sharing.Of 167 HIVTR candidates, 24 died (14.4%); this mortality rate was similar to that of controls (88/792, 11.1%, P = .30) with no significant difference in causes of mortality. A significantly lower proportion of HIVTR candidates (34.7%) underwent liver transplantation, compared with controls (47.6%, P = .003). In the combined cohort, baseline MELD score predicted pretransplantation mortality (hazard ratio [HR], 1.27; P < .0001), whereas HIV infection did not (HR, 1.69; P = .20). After controlling for pretransplantation CD4(+) cell count and HIV RNA levels, the only significant predictor of mortality in the HIV-infected subjects was pretransplantation MELD score (HR, 1.2; P < .0001).Pretransplantation mortality characteristics are similar between HIV-positive and HIV-negative candidates. Although lower CD4(+) cell counts and detectable levels of HIV RNA might be associated with a higher rate of pretransplantation mortality, baseline MELD score was the only significant independent predictor of pretransplantation mortality in HIV-infected liver transplant candidates.

  View details for DOI 10.1053/j.gastro.2009.09.053

  View details for Web of Science ID 000273427700026

  View details for PubMedID 19800334

  View details for PubMedCentralID PMC2826170

• Mycobacterium tuberculosis in Solid Organ Transplant Recipients AMERICAN JOURNAL OF TRANSPLANTATION Subramanian, A., Dorman, S. 2009; 9: S57-S62

  View details for DOI 10.1111/j.1600-6143.2009.02894.x

  View details for Web of Science ID 000272864500009

  View details for PubMedID 20070696

• Nontuberculous Mycobacteria in Solid Organ Transplant Recipients AMERICAN JOURNAL OF TRANSPLANTATION Dorman, S., Subramanian, A. 2009; 9: S63-S69

  View details for DOI 10.1111/j.1600-6143.2009.02895.x

  View details for Web of Science ID 000272864500010

  View details for PubMedID 20070697

• Detection and treatment of Strongyloides hyperinfection syndrome following lung transplantation TRANSPLANT INFECTIOUS DISEASE Balagopal, A., Mills, L., Shah, A., Subramanian, A. 2009; 11 (2): 149-154

  Abstract

  Strongyloides hyperinfection syndrome has not been reported in lung transplant recipients. We describe the case of a 61-year-old Peruvian man, who received bilateral lung transplants for idiopathic pulmonary fibrosis, and subsequently developed persistent fever with pulmonary infiltrates, ventilator dependence, and pneumothoraces. Bronchoalveolar lavage (BAL) cultures for bacteria, viruses, and fungi were negative, but testing for ova and parasites from BAL fluid revealed Strongyloides stercoralis larvae on day 16 post transplant. He was successfully treated with albendazole and ivermectin, and immunosuppression was reduced. BAL fluid also grew Mycobacterium kansasii, for which he received combination anti-mycobacterial therapy. This case illustrates the importance of screening for parasitic infections before transplantation in the appropriate clinical setting, and demonstrates the utility of direct diagnostic evaluation for parasitic infections in at-risk post-transplant patients with unexplained illnesses.

  View details for DOI 10.1111/j.1399-3062.2009.00375.x

  View details for Web of Science ID 000265015600010

  View details for PubMedID 19302281

• Renal Transplant in HIV-Positive Patients Long-term Outcomes and Risk Factors for Graft Loss ARCHIVES OF SURGERY Locke, J. E., Montgomery, R. A., Warren, D. S., Subramanian, A., Segev, D. L. 2009; 144 (1): 83-86

  Abstract

  In the highly active antiretroviral therapy era of improved survival for patients living with human immunodeficiency virus (HIV), chronic kidney disease now accounts for more than 10% of HIV-related deaths. The role of kidney transplant among HIV-positive patients with end-stage renal disease is under consideration, but concerns remain regarding allocation of kidneys to these patients when long-term benefit has not been firmly established. We evaluated 39,501 patients undergoing a renal transplant between January 1, 2004, and June 30, 2006, identified through the United Network for Organ Sharing national registry and found that, although long-term allograft survival is lower among HIV-positive recipients, controllable risk factors may explain this disparity. With proper donor selection and transplant recipient management, including the avoidance of prolonged cold ischemic time, use of living donors, and determination of optimal immunosuppression dosing before transplant, long-term graft survival comparable to that in HIV-negative patients can be achieved.

  View details for Web of Science ID 000262551400021

  View details for PubMedID 19153330

• Incidence and risk factors for hepatocellular carcinoma after solid organ transplantation TRANSPLANTATION Hoffmann, C. J., Subramanian, A. K., Cameron, A. M., Engels, E. A. 2008; 86 (6): 784-790

  Abstract

  Solid organ transplant recipients commonly are infected with hepatitis viruses, are immunosuppressed, and have other potential hepatocellular carcinoma (HCC) risk factors.We studied de novo HCC incidence arising after transplant using U.S. registry data (223,660 recipients, 1987-2005). We used proportional hazards regression to identify HCC risk factors and calculated standardized incidence ratios (SIRs) to compare HCC risk with that in the general population.Based on 74 cases reported by transplant centers to the registry, HCC incidence was 6.5 per 100,000 person-years among kidney, heart, and lung (non-liver) recipients and 25 per 100,000 person-years among liver recipients. Hepatocellular carcinoma incidence among non-liver recipients was independently associated with hepatitis B surface antigenemia (hazard ratio [HR] 9.7, 95% confidence interval [CI] 2.8-33), hepatitis C virus (HCV) infection (HR 6.9, 95% CI 2.5-19), and diabetes mellitus (HR 2.8, 95% CI 1.2-6.6). Among liver recipients, HCC incidence was associated with advancing age (P<0.001), male sex (HR 4.6, 95% CI 1.4-16), HCV infection (HR 3.1, 95% CI 1.3-7.2), and diabetes mellitus (HR 2.7, 95% CI 1.2-6.2). Among non-liver recipients, overall HCC incidence was similar to the general population (SIR 0.8) but elevated among those with HCV (3.4) or hepatitis B surface antigenemia (6.5). Hepatocellular carcinoma incidence among liver transplant recipients was elevated overall (SIR 3.4) and especially among those with HCV (5.0) or diabetes mellitus (6.2).Hepatocellular carcinoma incidence is elevated among liver transplant recipients and subsets of non-liver recipients. These risk factors indicate the need for improved control of viral hepatitis after solid organ transplantation.

  View details for DOI 10.1097/TP.0b013e3181837761

  View details for Web of Science ID 000259594600007

  View details for PubMedID 18813102

  View details for PubMedCentralID PMC2714173

• The high-risk donor: viral infections in solid organ transplantation CURRENT OPINION IN ORGAN TRANSPLANTATION Singer, A. L., Kucirka, L. M., Namuyinga, R., Hanrahan, C., Subramanian, A. K., Segev, D. L. 2008; 13 (4): 400-404

  Abstract

  Recently, four organ recipients were infected with HIV through transplantation, raising questions about current serologic testing policies. Currently, the decision to use enzyme-linked immunosorbent assay or nucleic acid testing, an expensive and time-consuming method capable of detecting more recent infections, is left up to individual organ procurement organizations. The purpose of this review was to present estimates of the window period between infection and detection by enzyme-linked immunosorbent assay and nucleic acid testing for HIV, hepatitis B virus, and hepatitis C virus; and to evaluate the impact of those infections on posttransplant outcomes.Nucleic acid testing for HIV can detect infections 12-13 days earlier than enzyme-linked immunosorbent assay; in the case of hepatitis B virus, infections are detected 21.8-36 days earlier; and in the case of hepatitis C virus, infections are detected 26-60 days earlier. Studies indicate that it is possible to manage all three infections posttransplant. HIV/hepatitis C virus coinfections seem to present the greatest posttransplant management challenges due to drug toxicities.Nucleic acid testing can reduce the window period and thus increase the probability of detecting viral infections. HIV, hepatitis B virus, and hepatitis C virus positive organs may be appropriate for use in some situations; nucleic acid testing helps patients and physicians make informed decisions about their use.

  View details for Web of Science ID 000258258500012

  View details for PubMedID 18685336

• Should a prisoner be placed on the organ transplant waiting list? The virtual mentor : VM Cameron, A. M., Subramanian, A. K., Sulkowski, M. S., Thomas, D. L., Nelson, K. E. 2008; 10 (2): 88-91

  View details for DOI 10.1001/virtualmentor.2008.10.2.ccas2-0802

  View details for PubMedID 23206819

• West Nile virus encephalitis in a kidney transplant recipient AMERICAN JOURNAL OF TRANSPLANTATION Shepherd, J. C., Subramanian, A., Montgomery, R. A., Samaniego, M. D., Gong, G., Bergmann, A., Blythe, D., Dropulic, L. 2004; 4 (5): 830-833

  Abstract

  We describe a case of West Nile virus encephalitis in a 54-year-old kidney transplant recipient. The clinical course was rapid and fatal. Serial CSF samples showed an evolving mononuclear pleiocytosis and serial MRIs showed increasing signs of cytotoxic edema in her basal ganglia. Seroepidemiological testing indicated that the infection was most likely acquired from transfusion of fresh frozen plasma at the time of transplantation.

  View details for DOI 10.1111/j.1600-6143.2004.00410.x

  View details for Web of Science ID 000221223900026

  View details for PubMedID 15084182

• Correlation of Chlamydia pneumoniae infection and severity of accelerated graft arteriosclerosis after cardiac transplantation TRANSPLANTATION Subramanian, A. K., Quinn, T. C., Kickler, T. S., Kasper, E. K., Tucker, P. C. 2002; 73 (5): 761-764

  Abstract

  Chlamydia pneumoniae has been associated with atherosclerosis, although its role in the process is not clearly defined. Heart transplant recipients are known to have high titers of antibodies to C. pneumoniae, and the organism has been recovered from the coronary arteries of both transplant recipients and donors. This study evaluated association between C. pneumoniae infection and accelerated graft arteriosclerosis (AGA), also known as cardiac allograft vasculopathy (CAV), after cardiac transplantation.A case-control study was performed with 54 heart transplant recipients at the Johns Hopkins Hospital. Severe cases had >50% luminal narrowing on cardiac catheterization, mild cases <50% narrowing, and controls were free of arteriosclerotic disease. Blood specimens were examined for C. pneumoniae serology and DNA detection by polymerase chain reaction (PCR) assays.For every twofold increase in geometric mean C. pneumoniae immunoglobulin (Ig)G titer, the odds ratio for severe AGA versus controls was 3.13 (P=0.03) and for mild AGA versus control patients was 1.61 (P=0.45). On Kaplan-Meier survival analysis there was a nonsignificant trend toward faster development of CAV in patients with higher C. pneumoniae antibody titers. Overall, 29% of heart transplant patients evaluated had evidence of circulating C. pneumoniae DNA by PCR, without a statistical difference between groups.C. pneumoniae IgG titer correlates with severity of allograft arteriosclerosis after cardiac transplantation. Circulating C. pneumoniae DNA is detectable by PCR in up to 30% of cardiac transplant recipients, but this does not correlate with severity of allograft vasculopathy.

  View details for Web of Science ID 000174717100018

  View details for PubMedID 11907424

• Cutaneous zygomycosis (mucormycosis) NEW ENGLAND JOURNAL OF MEDICINE Carpenter, C. F., Subramanian, A. K. 1999; 341 (25): 1891-1891

  View details for Web of Science ID 000084210200004

• Images in clinical medicine. Cutaneous zygomycosis (Mucormycosis). New England journal of medicine Carpenter, C. F., Subramanian, A. K. 1999; 341 (25): 1891-?

  View details for PubMedID 10601508