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Adriana E. Kajon - One of the best experts on this subject based on the ideXlab platform.

  • Outcomes of Human Adenovirus Infection and disease in a retrospective cohort of pediatric solid organ transplant recipients.
    Pediatric transplantation, 2019
    Co-Authors: Craig L K Boge, Brian T. Fisher, Hans Petersen, Alix E. Seif, Dale R. Purdy, Despoina M Galetaki, Richard L. Hodinka, Ana María Cárdenas, Adriana E. Kajon
    Abstract:

    Information about HAdV Infection in SOT recipients is limited. We aimed to describe HAdV Infection epidemiology and outcomes in a single-center retrospective cohort during the era of PCR availability. SOT recipients transplanted at the CHOP 2004-2013 were followed up for 180 days post-transplant. HAdV Infection was defined as a positive HAdV PCR from a clinical specimen. HAdV disease was defined by organ-specific radiologic and/or laboratory abnormalities. No HAdV surveillance protocols were employed during the study period; testing was solely per clinician discretion. Progression of HAdV Infection was defined as HAdV disease or ≥1-log viral load increase since a corresponding site's first positive specimen. Of the assembled 425 SOT recipients, 227 (52.6%) had ≥1 HAdV PCR. Twenty-four (10.6%) had ≥1 HAdV-positive PCR. HAdV-positive subjects were younger than uninfected subjects (2.0 years vs 6.5, P = 0.001). Infection incidence rates were highest in liver recipients (15.3%), followed by heart (8.6%), kidney (8.3%), and lung (4.2%). Four subjects (16.7%) met HAdV disease criteria at virus detection. Five subjects (20.8%) had progression of HAdV Infection. All-cause mortality rates in positive and negative subjects were 0% and 3.9%, respectively. HAdV Infection was infrequently detected in SOT recipients. Over one-third of HAdV-positive patients met disease criteria at detection or had Infection progression, but none died. This low all-cause mortality raises questions about benefits of HAdV surveillance. Larger multicenter studies are needed to assess incidence variance by center and comparative effectiveness of therapeutic interventions.

  • Outcomes of Human Adenovirus Infection and Disease in a Retrospective Cohort of Pediatric Hematopoietic Cell Transplant Recipients
    Journal of the Pediatric Infectious Diseases Society, 2018
    Co-Authors: Brian T. Fisher, Craig L K Boge, Hans Petersen, Alix E. Seif, Dale R. Purdy, Richard L. Hodinka, Ana María Cárdenas, Matthew Bryan, Brandon Loudon, Adriana E. Kajon
    Abstract:

    BACKGROUND Human Adenoviruses (HAdVs) are associated with significant morbidity and death after hematopoietic cell transplantation (HCT). In this study, we sought to determine the incidence of HAdV Infection among pediatric HCT recipients in the polymerase chain reaction (PCR) testing era, identify risk factors for viremia among patients undergoing HAdV surveillance, and assess the effectiveness of preemptive cidofovir. METHODS A single-center retrospective cohort of patients who underwent a transplant within a 10-year period was assembled. The incidence of and outcomes of patients with HAdV Infection and disease were determined by PCR results and chart review. A Cox regression model was used for surveilled allogeneic HCT recipients to identify factors associated with viremia. We also used a discrete-time failure model with inverse probability treatment weights to assess the effectiveness of preemptive cidofovir for Infection. RESULTS Among 572 HCT recipients, 76 (13.3%) had ≥1 sample that was HAdV PCR positive (3.5% of autologous HCT recipients and 19.7% of allogeneic HCT recipients). Among 191 allogeneic HCT recipients under surveillance, 58 (30.4%) had HAdV detected from any source, and 50 (26.2%) specifically had viremia. The mortality rate was higher in allogeneic HCT recipients with HAdV Infection versus those without Infection (25.9% vs 11.3%; P = .01). Factors associated with Infection included an age of 6 to 12 years, an absolute lymphocyte count of

  • Human Adenovirus Infection in kawasaki disease a confounding bystander
    Clinical Infectious Diseases, 2013
    Co-Authors: Preeti Jaggi, Adriana E. Kajon, Asuncion Mejias, Octavio Ramilo, Amy Leber
    Abstract:

    (See the Editorial Commentary by Rowley and Shulman, on pages 65–6.) Kawasaki disease (KD) is a febrile vasculitis of unknown etiology and represents the most common cause of pediatric acquired heart disease in the developed world. In the United States the estimated annual incidence of KD is approximately 10–21 per 100 000 children aged <5 years [1–3]. Given the clinical similarities, Human Adenovirus (HAdV) Infection is one of the most frequent conditions included in the differential diagnosis when considering KD [4]. Recent studies show that up to 8.8% of children treated for KD have respiratory viruses identified in the upper respiratory tract, including a patient with HAdV Infection who eventually developed coronary artery aneurysm [5]. HAdV has also been isolated from a lymph node in a patient with fatal KD [6]. The introduction of highly sensitive molecular methods allows for enhanced detection of HAdV in the upper respiratory tract. However, few data are available regarding frequency, viral load, and types of HAdV in KD patients. HAdVs belong to the Adenoviridae family and are divided into 7 subgroups designated “species” (A–G) according to their immunologic, biologic, and biochemical characteristics [7]. Primary Infections with species C (HAdV-C) occur commonly in children younger than age 5; in addition to primary Infection, HAdV-C (especially serotypes 1, 2, and 5) can also persist in pediatric tonsils for years with low-grade replication [8]. The present study was designed to determine whether there are differences in the nasopharyngeal (NP)/throat HAdV burden as indicated by semiquantitative cycle thresholds (Cts) between children determined to have HAdV disease (with some KD-like features) vs those determined to have KD with incidental detection of HAdV, and to determine if HAdV-C shedding may be occurring in patients with KD.

  • Human Adenovirus Infection in Kawasaki Disease: A Confounding Bystander?
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2012
    Co-Authors: Preeti Jaggi, Adriana E. Kajon, Asuncion Mejias, Octavio Ramilo, Amy Leber
    Abstract:

    (See the Editorial Commentary by Rowley and Shulman, on pages 65–6.) Kawasaki disease (KD) is a febrile vasculitis of unknown etiology and represents the most common cause of pediatric acquired heart disease in the developed world. In the United States the estimated annual incidence of KD is approximately 10–21 per 100 000 children aged

  • Genotype Prevalence and Risk Factors for Severe Clinical Adenovirus Infection, United States 2004–2006
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2007
    Co-Authors: Gregory C. Gray, Adriana E. Kajon, Troy A. Mccarthy, Mark G. Lebeck, David P. Schnurr, Kevin L. Russell, Marie L. Landry, Diane S. Leland, Gregory A. Storch, Christine C. Ginocchio
    Abstract:

    More than 35 years ago, population-based studies of viral respiratory illnesses among US families were conducted in Ohio [1], Kansas [2], Louisiana [3], New York [4], and Washington [5]. As a result of these investigations, scientists concluded that Adenovirus Infection was quite common among children. Approximately 50% of Infections were asymptomatic, and symptomatic Infections were typically mild and resolved without sequelae. In contrast, military populations experienced severe epidemics of acute respiratory disease, including pneumonia and encephalitis, especially involving Adenovirus types 4, 7, and 21. For example, in 1958, adenoviral Infection was reported to have caused hospitalization of an estimated 10% of military recruits [6] and to be the etiology of most respiratory disease during winter months. Subsequently, vaccines for Adenovirus types 4 and 7 were developed and effectively used among US military trainees from the 1970s until the late 1990s [7, 8]. Thus, until recently, Adenovirus Infection was considered to have little consequence, except for causing morbidity among military trainees. However, much has changed since these early epidemiological studies were conducted. In contrast to the modest number of Adenovirus types recognized 35 years ago, 51 unique serotypes are now recognized. Different serotypes have been found to have different tissue tropisms that correlate with different clinical manifestations of Infection. Limited epidemiological investigations have revealed that, among some specific serotypes, multiple genetic variants exist that often have quite different geographical distributions and associated virulence [9-11]. In addition, largely because of molecular diagnostics, Adenovirus Infection has been associated with a number of acute and chronic diseases, including chronic airway obstruction [12] and pulmonary dysplasia [13], myocarditis and dilated cardiomyopathy [14], mononucleosis-like syndromes [15], intussusception [16], sudden infant perinatal death [17], and obesity [18, 19]. Among some population groups, adenoviral Infection is common and, often, severe. For example, the incidence of adenoviral disease among bone marrow transplant recipients varies from 3% to 20% [20], and mortality can exceed 50% [21]. Similarly, multiple recent outbreaks of adenoviral Infection in the United States have frequently occurred among institutionalized children and in medical settings, resulting in significant morbidity and mortality among patients and medical staff [22]. In vitro studies suggest that specific Adenovirus types are more likely to respond to certain antiviral therapies [23]. Finally, since the military lost its manufacturer of Adenovirus types 4 and 7 vaccines in the late 1990s, numerous outbreaks of Adenovirus Infection have occurred among military trainees, resulting in great morbidity [24, 25]. Subsequently, the US Department of Defense identified a new vaccine manufacturer, and restoration of Adenovirus types 4 and 7 vaccines is projected for 2008 [25]. It seems prudent to investigate whether previously very effective and safe vaccines may also benefit some nonmilitary populations. Therefore, an updated look at the epidemiology of Human Adenovirus Infection is warranted. In this report, we present 25 months of viral and patient epidemiological data on clinical Adenovirus Infection detected through a nationwide network of 22 US military and civilian medical facilities. We used a recently described molecular Adenovirus typing technique to characterize the strains of Adenovirus [26].

William S. M. Wold - One of the best experts on this subject based on the ideXlab platform.

  • Generation and characterization of an Il2rg knockout Syrian hamster model for XSCID and HAdV-C6 Infection in immunocompromised patients.
    Disease models & mechanisms, 2020
    Co-Authors: Baoling Ying, Jacqueline F. Spencer, Ann E. Tollefson, William S. M. Wold, Yanan Liu, Jinxin Miao, James D. Brien, Yaohe Wang, Zhongde Wang
    Abstract:

    ABSTRACT Model animals are indispensable for the study of Human diseases, and in general, of complex biological processes. The Syrian hamster is an important model animal for infectious diseases, behavioral science and metabolic science, for which more experimental tools are becoming available. Here, we describe the generation and characterization of an interleukin-2 receptor subunit gamma (Il2rg) knockout (KO) Syrian hamster strain. In Humans, mutations in IL2RG can result in a total failure of T and natural killer (NK) lymphocyte development and nonfunctional B lymphocytes (X-linked severe combined immunodeficiency; XSCID). Therefore, we sought to develop a non-murine model to study XSCID and the infectious diseases associated with IL2RG deficiency. We demonstrated that the Il2rg KO hamsters have a lymphoid compartment that is greatly reduced in size and diversity, and is impaired in function. As a result of the defective adaptive immune response, Il2rg KO hamsters developed a more severe Human Adenovirus Infection and cleared virus less efficiently than immune competent wild-type hamsters. Because of this enhanced virus replication, Il2rg KO hamsters developed more severe Adenovirus-induced liver pathology than wild-type hamsters. This novel hamster strain will provide researchers with a new tool to investigate Human XSCID and its related Infections.

  • Anti-adenoviral Artificial MicroRNAs Expressed from AAV9 Vectors Inhibit Human Adenovirus Infection in Immunosuppressed Syrian Hamsters.
    Molecular therapy. Nucleic acids, 2017
    Co-Authors: Katrin Schaar, Anja Geisler, Milena Kraus, Sandra Pinkert, Markian Pryshliak, Jacqueline F. Spencer, Ann E. Tollefson, Baoling Ying, Jens Kurreck, William S. M. Wold
    Abstract:

    Infections of immunocompromised patients with Human Adenoviruses (hAd) can develop into life-threatening conditions, whereas drugs with anti-adenoviral efficiency are not clinically approved and have limited efficacy. Small double-stranded RNAs that induce RNAi represent a new class of promising anti-adenoviral therapeutics. However, as yet, their efficiency to treat hAd5 Infections has only been investigated in vitro. In this study, we analyzed artificial microRNAs (amiRs) delivered by self-complementary adeno-associated virus (scAAV) vectors for treatment of hAd5 Infections in immunosuppressed Syrian hamsters. In vitro evaluation of amiRs targeting the E1A, pTP, IVa2, and hexon genes of hAd5 revealed that two scAAV vectors containing three copies of amiR-pTP and three copies of amiR-E1A, or six copies of amiR-pTP, efficiently inhibited hAd5 replication and improved the viability of hAd5-infected cells. Prophylactic application of amiR-pTP/amiR-E1A- and amiR-pTP-expressing scAAV9 vectors, respectively, to immunosuppressed Syrian hamsters resulted in the reduction of hAd5 levels in the liver of up to two orders of magnitude and in reduction of liver damage. Concomitant application of the vectors also resulted in a decrease of hepatic hAd5 Infection. No side effects were observed. These data demonstrate anti-adenoviral RNAi as a promising new approach to combat hAd5 Infection.

  • stat2 knockout syrian hamsters support enhanced replication and pathogenicity of Human Adenovirus revealing an important role of type i interferon response in viral control
    PLOS Pathogens, 2015
    Co-Authors: Karoly Toth, Jacqueline F. Spencer, Ann E. Tollefson, Baoling Ying, Zhongde Wang, John E Sagartz, Ilkeun Kong, William S. M. Wold
    Abstract:

    Human Adenoviruses have been studied extensively in cell culture and have been a model for studies in molecular, cellular, and medical biology. However, much less is known about Adenovirus replication and pathogenesis in vivo in a permissive host because of the lack of an adequate animal model. Presently, the most frequently used permissive immunocompetent animal model for Human Adenovirus Infection is the Syrian hamster. Species C Human Adenoviruses replicate in these animals and cause pathology that is similar to that seen with Humans. Here, we report findings with a new Syrian hamster strain in which the STAT2 gene was functionally knocked out by site-specific gene targeting. Adenovirus-infected STAT2 knockout hamsters demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs of STAT2 knockout animals was 100- to 1000-fold higher than that in wild-type hamsters. Notably, the adaptive immune response to Adenovirus is not adversely affected in STAT2 knockout hamsters, and surviving hamsters cleared the Infection by 7 to 10 days post challenge. We show that the Type I interferon pathway is disrupted in these hamsters, revealing the critical role of interferon-stimulated genes in controlling Adenovirus Infection. This is the first study to report findings with a genetically modified Syrian hamster infected with a virus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting Human Adenovirus replication in a permissive animal model. Besides providing an insight into Adenovirus Infection in Humans, our results are also interesting from the perspective of the animal model: STAT2 knockout Syrian hamster may also be an important animal model for studying other viral Infections, including Ebola-, hanta-, and dengue viruses, where Type I interferon-mediated innate immunity prevents wild type hamsters from being effectively infected to be used as animal models.

  • 1018. Immune-Competent Cotton Rat Animal Model for Evaluation of Oncolytic Adenoviruses
    Molecular Therapy, 2004
    Co-Authors: Karoly Toth, Jacqueline F. Spencer, Ann E. Tollefson, Mohan Kuppuswamy, Konstantin Doronin, Drew L. Lichtenstein, William S. M. Wold
    Abstract:

    Adenoviruses as oncolytic vectors have been investigated for almost a decade, and show great promise for the treatment of cancer. These vectors kill tumor cells as a result of the lytic replication cycle of the virus. A significant impediment to research with replicating Adenovirus vectors is the lack of suitable animal models. As Adenoviruses are very species-specific, researchers studying vectors based on Human Adenovirus 5 were forced to use the highly artificial immunodeficient mouse-Human tumor xenograft model, where the viruses could replicate within the Human tumor cells. In this system, the replication of the Adenovirus vector in normal tissues and the effect of the host immune system on the anti-tumor activity of the vector cannot be studied. We have developed an immunocompetent, semi-permissive animal model to study oncolytic Adenovirus vectors. In this model, we induced subcutaneous tumors in immunocompetent cotton rats by injecting the animals with a suspension of LCRT cotton rat sarcoma cells. The cotton rat was shown by others to be semi-permissive to Human Adenovirus Infection, and to exhibit pathology similar to that observed in Humans with respiratory adenoviral Infection. The LCRT cell line is derived from a spontaneously arisen mammary tumor. These cells support Human Adenovirus replication in vitro, as evidenced by expression of adenoviral late proteins and the production of progeny virus that can initiate a new infectious cycle. As a result, LCRT cells are destroyed upon Infection even with low multiplicities of virus. When injected subcutaneously into cotton rats, LCRT cells form rapidly growing subcutaneous tumors that metastasize to the lung and to various lymph nodes. They show the characteristics of fibrosarcoma tumors, and usually contain a large necrotic center and rapidly dividing cells at the periphery. We injected pre-existing or nascent subcutaneous LCRT tumors with VRX-007, an oncolytic Adenovirus overexpressing ADP. ADP is an adenoviral protein expressed at the culmination of Infection that facilitates cell lysis and virus egress, thus speeding up the cell-to-cell dissemination of the vector. Injection of intact VRX-007 consistently caused a significant delay in tumor growth, while tumors injected with UV inactivated vector grew at a rate similar to that of vehicle injected tumors. We have also established the intravenous maximum tolerated dose of VRX-007 in cotton rats. Based upon these results, we propose subcutaneous LCRT tumor bearing cotton rats as a novel, immunocompetent, semi-permissive animal model for the testing of oncolytic Adenovirus vectors.

Inci Yildirim - One of the best experts on this subject based on the ideXlab platform.

  • #18: Brincidofovir for the Treatment of Disseminated Human Adenovirus Infection in Pediatric Solid-organ Transplant Recipients
    Journal of the Pediatric Infectious Diseases Society, 2021
    Co-Authors: Jackson Londeree, Pamela D. Winterberg, Rouba Garro, Stella Shin, Rochelle Liverman, Anastacia Serluco, Rene Romero, Roshan George, Inci Yildirim
    Abstract:

    Abstract Background Human Adenovirus (HAdV) viremia can cause significant morbidity among pediatric patients undergoing solid-organ transplantation (SOT). Currently, there are no US Food and Drug Administration (FDA)-approved treatments for HAdV Infections, and historically the mainstay of treatment has been decreasing immunosuppression with antiviral therapies reserved for those with severe disease. Brincidofovir (BCV) is an investigational antiviral drug with potency against HAdV. We describe four cases of disseminated HAdV Infection treated with (BCV) among pediatric SOT patients. Methods We retrospectively reviewed 4 cases of severe disseminated HAdV Infection, which occurred between 2018 and 2019, in a tertiary pediatric transplant center. HAdV Infection was defined as a positive HAdV PCR from a clinical specimen. Baseline clinical characteristics, disease course, treatment, and outcomes were reviewed. Results Four pediatric SOT patients (2 kidneys, 1 dual kidney/liver, and 1 liver) ranging in age from 9 months to 19 years were diagnosed with HAdV Infection (Table 1). Patients presented with varied symptoms from 12 to 912 days post-transplant. Peak HAdV viral load ranged from 37,000 to &gt;1,000,000 copies/mL. All patients had disseminated disease with evidence of graft involvement and varying degrees of acute kidney injury (AKI) making them candidates for BCV therapy over cidofovir to avoid nephrotoxicity. Three out of four patients received cidofovir prior to conversion to BCV. IRB-approved compassionate use of BCV was dosed at 2 mg/kg (max 100 mg) twice weekly PO along with reduced immunosuppression. Resolution of symptoms and HAdV viremia was seen at a mean of 21.5 days (range 15–32) of therapy. All patients had resolution of AKI with a return to baseline creatinine after therapy. Conclusions Though HAdV Infection in pediatric SOT patients is uncommon, a subset of patients experience severe disease, morbidity, and graft loss. Currently, HAdV is not routinely monitored in pediatric SOT transplant patients. Although supportive care and decreased immunosuppression remain as the most important component of therapy, BCV was well tolerated and efficacious in our series. Further research is needed to better understand risk factors for HAdV Infection and potential antiviral treatment options to improve patient outcomes.

  • Brincidofovir for the treatment of Human Adenovirus Infection in pediatric solid organ transplant recipients: A case series.
    Pediatric Transplantation, 2020
    Co-Authors: Jackson Londeree, Pamela D. Winterberg, Rouba Garro, Roshan P. George, Stella Shin, Rochelle Liverman, Anastacia Serluco, Rene Romero, Inci Yildirim
    Abstract:

    HAdV viremia can cause significant morbidity among pediatric recipients of SOT with variability in incidence and severity of disease based on the type of allograft. Currently, there are no US FDA-approved treatments for HAdV Infections, and historically, the mainstay of treatment has been decreasing immunosuppression, with antiviral therapies reserved for those with severe disease. We describe the treatment of four pediatric SOT recipients (two kidney, one combined kidney-liver, and one liver) presenting with HAdV disease at our institution using brincidofovir. Our case series highlights the variability in presentation and the potential for severe disease in pediatric SOT recipients as we review disease presentation, disease course, complications, and treatment with brincidofovir.

Yong Poovorawan - One of the best experts on this subject based on the ideXlab platform.

  • Molecular characterization of Human Adenovirus Infection in Thailand, 2009–2012
    Virology Journal, 2013
    Co-Authors: Punsinee Sriwanna, Thaweesak Chieochansin, Chanpim Vuthitanachot, Viboonsuk Vuthitanachot, Apiradee Theamboonlers, Yong Poovorawan
    Abstract:

    Background Human Adenovirus (HAdV) can cause a wide spectrum of Human diseases worldwide. Methods Using PCR and sequence analysis, we investigated HAdV Infection prevalence in the Thai population for four years from January 2009 to December 2012. We collected Nasopharyngeal swab/aspirate (NP) specimens from patients in Bangkok, Khon Kaen, and Nakhon Si Thammarat province and fecal specimens only from Bangkok and Khon Kaen province. Results We observed HAdV Infection in 1.04% (82/7,921) of NP samples and in 5.84% (76/1,301) of fecal specimens. HAdV-B3 (32%) and HAdV-C1 (31%) were the genotypes most commonly associated with NP specimens followed by HAdV-C2 (13%) and HAdV-C5 (12%). In fecal specimens, we found that 25% harbored HAdV-F41 followed by HAdV-C1 (18%), HAdV-C2 (16%), and HAdV-B3 (13%). Out of all population subsets, children below the age of 3 years were the most likely to be HAdV positive (63.29%). In addition, HAdV Infection occurred throughout the year without a seasonal distribution pattern, although HAdV Infection of NP samples peaked from January-April while HAdV Infection peaked from January to March and then again from May to July in fecal samples. Conclusions This study has for the first time reported the HAdV Infection rate in Thai NP and fecal specimens from 2009–2012. We observed that HAdV-B3 and HAdV-C1 were commonly found in NP specimens, and that HAdV-F41 was the most prevalence in fecal specimens in Thailand during the study period.

  • molecular characterization of Human Adenovirus Infection in thailand 2009 2012
    Virology Journal, 2013
    Co-Authors: Punsinee Sriwanna, Thaweesak Chieochansin, Chanpim Vuthitanachot, Viboonsuk Vuthitanachot, Apiradee Theamboonlers, Yong Poovorawan
    Abstract:

    Background: Human Adenovirus (HAdV) can cause a wide spectrum of Human diseases worldwide. Methods: Using PCR and sequence analysis, we investigated HAdV Infection prevalence in the Thai population for four years from January 2009 to December 2012. We collected Nasopharyngeal swab/aspirate (NP) specimens from patients in Bangkok, Khon Kaen, and Nakhon Si Thammarat province and fecal specimens only from Bangkok and Khon Kaen province. Results: We observed HAdV Infection in 1.04% (82/7,921) of NP samples and in 5.84% (76/1,301) of fecal specimens. HAdV-B3 (32%) and HAdV-C1 (31%) were the genotypes most commonly associated with NP specimens followed by HAdV-C2 (13%) and HAdV-C5 (12%). In fecal specimens, we found that 25% harbored HAdV-F41 followed by HAdV-C1 (18%), HAdV-C2 (16%), and HAdV-B3 (13%). Out of all population subsets, children below the age of 3 years were the most likely to be HAdV positive (63.29%). In addition, HAdV Infection occurred throughout the year without a seasonal distribution pattern, although HAdV Infection of NP samples peaked from January-April while HAdV Infection peaked from January to March and then again from May to July in fecal samples. Conclusions: This study has for the first time reported the HAdV Infection rate in Thai NP and fecal specimens from 2009–2012. We observed that HAdV-B3 and HAdV-C1 were commonly found in NP specimens, and that HAdV-F41 was the most prevalence in fecal specimens in Thailand during the study period.

Ana María Cárdenas - One of the best experts on this subject based on the ideXlab platform.

  • outcomes of Human Adenovirus Infection and disease in a retrospective cohort of pediatric hematopoietic cell transplant recipients
    Journal of the Pediatric Infectious Diseases Society, 2019
    Co-Authors: Brian T. Fisher, Craig L K Boge, Hans Petersen, Alix E. Seif, Dale R. Purdy, Richard L. Hodinka, Ana María Cárdenas, Matthew Bryan, Brandon Loudon
    Abstract:

    BACKGROUND Human Adenoviruses (HAdVs) are associated with significant morbidity and death after hematopoietic cell transplantation (HCT). In this study, we sought to determine the incidence of HAdV Infection among pediatric HCT recipients in the polymerase chain reaction (PCR) testing era, identify risk factors for viremia among patients undergoing HAdV surveillance, and assess the effectiveness of preemptive cidofovir. METHODS A single-center retrospective cohort of patients who underwent a transplant within a 10-year period was assembled. The incidence of and outcomes of patients with HAdV Infection and disease were determined by PCR results and chart review. A Cox regression model was used for surveilled allogeneic HCT recipients to identify factors associated with viremia. We also used a discrete-time failure model with inverse probability treatment weights to assess the effectiveness of preemptive cidofovir for Infection. RESULTS Among 572 HCT recipients, 76 (13.3%) had ≥1 sample that was HAdV PCR positive (3.5% of autologous HCT recipients and 19.7% of allogeneic HCT recipients). Among 191 allogeneic HCT recipients under surveillance, 58 (30.4%) had HAdV detected from any source, and 50 (26.2%) specifically had viremia. The mortality rate was higher in allogeneic HCT recipients with HAdV Infection versus those without Infection (25.9% vs 11.3%; P = .01). Factors associated with Infection included an age of 6 to 12 years, an absolute lymphocyte count of <200 cells/μL, recent prednisone exposure, and recent bacteremia. Preemptive cidofovir was not associated with a reduced risk of Infection progression (odds ratio, 0.96 [95% confidence interval, 0.30-3.05]). CONCLUSIONS HAdV Infection is common and associated with an increased rate of death after allogeneic HCT. Using prediction models that incorporate factors associated with HAdV might help target surveillance. Preemptive cidofovir therapy was not protective in a subset of HAdV-positive patients. Larger observational or randomized investigations are necessary, because the utility of surveillance requires effective preemptive therapies.

  • Outcomes of Human Adenovirus Infection and disease in a retrospective cohort of pediatric solid organ transplant recipients.
    Pediatric transplantation, 2019
    Co-Authors: Craig L K Boge, Brian T. Fisher, Hans Petersen, Alix E. Seif, Dale R. Purdy, Despoina M Galetaki, Richard L. Hodinka, Ana María Cárdenas, Adriana E. Kajon
    Abstract:

    Information about HAdV Infection in SOT recipients is limited. We aimed to describe HAdV Infection epidemiology and outcomes in a single-center retrospective cohort during the era of PCR availability. SOT recipients transplanted at the CHOP 2004-2013 were followed up for 180 days post-transplant. HAdV Infection was defined as a positive HAdV PCR from a clinical specimen. HAdV disease was defined by organ-specific radiologic and/or laboratory abnormalities. No HAdV surveillance protocols were employed during the study period; testing was solely per clinician discretion. Progression of HAdV Infection was defined as HAdV disease or ≥1-log viral load increase since a corresponding site's first positive specimen. Of the assembled 425 SOT recipients, 227 (52.6%) had ≥1 HAdV PCR. Twenty-four (10.6%) had ≥1 HAdV-positive PCR. HAdV-positive subjects were younger than uninfected subjects (2.0 years vs 6.5, P = 0.001). Infection incidence rates were highest in liver recipients (15.3%), followed by heart (8.6%), kidney (8.3%), and lung (4.2%). Four subjects (16.7%) met HAdV disease criteria at virus detection. Five subjects (20.8%) had progression of HAdV Infection. All-cause mortality rates in positive and negative subjects were 0% and 3.9%, respectively. HAdV Infection was infrequently detected in SOT recipients. Over one-third of HAdV-positive patients met disease criteria at detection or had Infection progression, but none died. This low all-cause mortality raises questions about benefits of HAdV surveillance. Larger multicenter studies are needed to assess incidence variance by center and comparative effectiveness of therapeutic interventions.

  • Outcomes of Human Adenovirus Infection and Disease in a Retrospective Cohort of Pediatric Hematopoietic Cell Transplant Recipients
    Journal of the Pediatric Infectious Diseases Society, 2018
    Co-Authors: Brian T. Fisher, Craig L K Boge, Hans Petersen, Alix E. Seif, Dale R. Purdy, Richard L. Hodinka, Ana María Cárdenas, Matthew Bryan, Brandon Loudon, Adriana E. Kajon
    Abstract:

    BACKGROUND Human Adenoviruses (HAdVs) are associated with significant morbidity and death after hematopoietic cell transplantation (HCT). In this study, we sought to determine the incidence of HAdV Infection among pediatric HCT recipients in the polymerase chain reaction (PCR) testing era, identify risk factors for viremia among patients undergoing HAdV surveillance, and assess the effectiveness of preemptive cidofovir. METHODS A single-center retrospective cohort of patients who underwent a transplant within a 10-year period was assembled. The incidence of and outcomes of patients with HAdV Infection and disease were determined by PCR results and chart review. A Cox regression model was used for surveilled allogeneic HCT recipients to identify factors associated with viremia. We also used a discrete-time failure model with inverse probability treatment weights to assess the effectiveness of preemptive cidofovir for Infection. RESULTS Among 572 HCT recipients, 76 (13.3%) had ≥1 sample that was HAdV PCR positive (3.5% of autologous HCT recipients and 19.7% of allogeneic HCT recipients). Among 191 allogeneic HCT recipients under surveillance, 58 (30.4%) had HAdV detected from any source, and 50 (26.2%) specifically had viremia. The mortality rate was higher in allogeneic HCT recipients with HAdV Infection versus those without Infection (25.9% vs 11.3%; P = .01). Factors associated with Infection included an age of 6 to 12 years, an absolute lymphocyte count of