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Kampouri E, Manuel O. Can Quantitative Polymerase Chain Reaction in Tissue Improve Cytomegalovirus Management? Balancing Diagnostic Sensitivity and the Risk of Overtreatment. Transpl Infect Dis 2025:e70045. [PMID: 40298360 DOI: 10.1111/tid.70045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2025] [Accepted: 04/14/2025] [Indexed: 04/30/2025]
Affiliation(s)
- Eleftheria Kampouri
- Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Oriol Manuel
- Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
- Transplantation Center, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
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2
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Kotton CN, Kumar D, Manuel O, Chou S, Hayden RT, Danziger-Isakov L, Asberg A, Tedesco-Silva H, Humar A. The Fourth International Consensus Guidelines on the Management of Cytomegalovirus in Solid Organ Transplantation. Transplantation 2025:00007890-990000000-01056. [PMID: 40200403 DOI: 10.1097/tp.0000000000005374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/10/2025]
Affiliation(s)
- Camille N Kotton
- Transplant and Immunocompromised Host Service, Infectious Diseases Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Deepali Kumar
- Division of Infectious Diseases, Department of Medicine, Ajmera Transplant Center and University of Toronto, Toronto, ON, Canada
| | - Oriol Manuel
- Infectious Diseases Service and Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland
| | - Sunwen Chou
- Division of Infectious Diseases, Oregon Health and Science University, Portland, OR
| | - Randall T Hayden
- Department of Pathology, St Jude Children's Research Hospital, Memphis, TN
| | - Lara Danziger-Isakov
- Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Anders Asberg
- Department of Transplantation Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway
| | | | - Atul Humar
- Division of Infectious Diseases, Department of Medicine, Ajmera Transplant Center and University of Toronto, Toronto, ON, Canada
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3
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McBee MK, Butani L. Post-transplant diarrhea in pediatric kidney transplant recipients. Pediatr Nephrol 2025:10.1007/s00467-024-06572-6. [PMID: 39907757 DOI: 10.1007/s00467-024-06572-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 10/02/2024] [Accepted: 10/03/2024] [Indexed: 02/06/2025]
Abstract
Diarrhea is a common complication after pediatric kidney transplantation. While mycophenolate mofetil is an important and common cause of post-transplant diarrhea, diarrhea can result from infectious and other non-infectious causes. Many complications can result from severe diarrhea including acute kidney injury from dehydration. Other unique complications in transplant recipients include tacrolimus toxicity and acute rejection (from changes in immunosuppressive pharmacokinetics or dosing in response to the diarrhea). Therefore, a thorough evaluation is recommended for all pediatric patients with severe diarrhea to ensure that appropriate interventions are instituted, and risks of complications minimized. Our review describes the scope of the morbidity of diarrheal illness after transplantation, common causes, and newer insights in the management of diarrhea, both supportive and targeted to the underlying cause.
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Affiliation(s)
- Machi Kaneko McBee
- Division of Pediatric Nephrology, Department of Pediatrics, University of California, Davis, 2516 Stockton Blvd, Sacramento, CA, 95817, USA.
| | - Lavjay Butani
- Division of Pediatric Nephrology, Department of Pediatrics, University of California, Davis, 2516 Stockton Blvd, Sacramento, CA, 95817, USA
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4
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Chung MC, Chen CH, Chang SS, Lee CY, Tian YC, Wu MY, Wang HH, Yu CC, Chen TW, Kao CC, Hsu CY, Chiang YJ, Wu MJ, Chen YT, Wu MS. Prevention and management of cytomegalovirus infection and disease in kidney transplant: A consensus statement of the Transplantation Society of Taiwan. J Formos Med Assoc 2025; 124:104-111. [PMID: 38777672 DOI: 10.1016/j.jfma.2024.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 03/24/2024] [Accepted: 05/14/2024] [Indexed: 05/25/2024] Open
Abstract
Kidney transplant recipients have an increased risk of cytomegalovirus (CMV) infection and disease. A strategy for mitigating the risk of CMV infection in kidney transplant recipients has not yet been established in Taiwan. The Transplantation Society of Taiwan aimed to develop a consensus by expert opinion on the prevention and management of CMV infection. Based on the results of Consensus Conference, we suggested low-dose valganciclovir prophylaxis (450 mg once daily) for kidney transplant recipients. The prophylaxis duration was ≥6 months for high-risk (D+/R-) patients and 3 months for moderate-risk (R+) patients. Even for low-risk (D-/R-) patients, prophylaxis for at least 3 months is recommended because of the high seroprevalence of CMV in Taiwan. CMV prophylaxis was suggested after anti-thymocyte globulin treatment but not after methylprednisolone pulse therapy. Routine surveillance after prophylaxis, secondary prophylaxis after CMV disease treatment, and mTOR inhibitors for primary CMV prophylaxis were not recommended. Letermovir and marabavir are emerging CMV agents used for prophylaxis and refractory CMV disease. CMV immunoglobulins have been used to treat refractory CMV disease in Taiwan. We hope this consensus will help professionals manage patients with CMV in Taiwan to improve the quality of care.
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Affiliation(s)
- Mu-Chi Chung
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taiwan; Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Cheng-Hsu Chen
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taiwan; Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Ph.D. Program in Tissue Engineering and Regenerative Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Life Science, Tunghai University, Taichung, Taiwan
| | - Shen-Shin Chang
- Division of Transplantation, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chih-Yuan Lee
- Department of Surgery, National Taiwan University Hospital, Taiwan
| | - Ya-Chung Tian
- Kidney Research Center and Department of Nephrology Linkou Chang Aging Memorial Hospital, Taiwan
| | - Mei-Yi Wu
- Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
| | - Hsu-Han Wang
- Department of Urology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chia-Cheng Yu
- Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Teng-Wei Chen
- Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chien-Chang Kao
- Division of Urology, Department of Surgery, Tri-service General Hospital, National Defense Medical, Taiwan
| | - Chih-Yang Hsu
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Taiwan
| | - Yang-Jen Chiang
- Department of Urology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Ming-Ju Wu
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taiwan; Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yen-Ta Chen
- Division of Urology, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Mai-Szu Wu
- Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
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5
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Castillo Almeida NE, Gomez CA. Acute diarrhea in the hospitalized immunocompromised patient: what is new on diagnostic and treatment? Curr Opin Crit Care 2024; 30:456-462. [PMID: 39034915 PMCID: PMC11377059 DOI: 10.1097/mcc.0000000000001191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/23/2024]
Abstract
PURPOSE OF REVIEW This article aims to provide an intuitive framework for diagnosing and managing healthcare-associated diarrhea (HCAD) in the immunocompromised (IC) host. RECENT FINDINGS Our understanding of diarrhea in hospitalized IC patients has significantly evolved. However, the challenge lies in distinguishing between these patients' numerous causes of diarrhea. The incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels has led to a paradigm shift in our approach to diarrhea. However, using these panels judiciously is of utmost importance, as their misuse can lead to over-testing, overtreatment, and increased hospital costs. We propose a stepwise diagnostic algorithm that ensures diagnostic stewardship, optimal patient care, and resource utilization. SUMMARY Diarrhea is a common complication in hospitalized IC patients and is associated with significant morbidity and rare mortality. The advent of new diagnostics, such as GI multiplex PCR panels, holds promise in facilitating the detection of recognized pathogens and may allow for improved outcomes using pathogen-targeted therapy.
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Affiliation(s)
- Natalia E Castillo Almeida
- Department of Internal Medicine, Division of Infectious Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA
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6
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Flynn TG, Olortegui MP, Kosek MN. Viral gastroenteritis. Lancet 2024; 403:862-876. [PMID: 38340741 DOI: 10.1016/s0140-6736(23)02037-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 08/17/2023] [Accepted: 09/18/2023] [Indexed: 02/12/2024]
Abstract
Since the discovery of norovirus in 1972 as a cause of what was contemporarily known as acute infectious non-bacterial gastroenteritis, scientific understanding of the viral gastroenteritides has continued to evolve. It is now recognised that a small number of viruses are the predominant cause of acute gastroenteritis worldwide, in both high-income and low-income settings. Although treatment is still largely restricted to the replacement of fluid and electrolytes, improved diagnostics have allowed attribution of illness, enabling both targeted treatment of individual patients and prioritisation of interventions for populations worldwide. Questions remain regarding specific genetic and immunological factors underlying host susceptibility, and the optimal clinical management of patients who are susceptible to severe or prolonged manifestations of disease. Meanwhile, the worldwide implementation of rotavirus vaccines has led to substantial reductions in morbidity and mortality, and spurred interest in vaccine development to diminish the impact of the most prevalent viruses that are implicated in this syndrome.
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Affiliation(s)
- Thomas G Flynn
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA
| | | | - Margaret N Kosek
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
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7
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Kreitmann L, Helms J, Martin-Loeches I, Salluh J, Poulakou G, Pène F, Nseir S. ICU-acquired infections in immunocompromised patients. Intensive Care Med 2024; 50:332-349. [PMID: 38197931 DOI: 10.1007/s00134-023-07295-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 11/25/2023] [Indexed: 01/11/2024]
Abstract
Immunocompromised patients account for an increasing proportion of the typical intensive care unit (ICU) case-mix. Because of the increased availability of new drugs for cancer and auto-immune diseases, and improvement in the care of the most severely immunocompromised ICU patients (including those with hematologic malignancies), critically ill immunocompromised patients form a highly heterogeneous patient population. Furthermore, a large number of ICU patients with no apparent immunosuppression also harbor underlying conditions altering their immune response, or develop ICU-acquired immune deficiencies as a result of sepsis, trauma or major surgery. While infections are associated with significant morbidity and mortality in immunocompromised critically ill patients, little specific data are available on the incidence, microbiology, management and outcomes of ICU-acquired infections in this population. As a result, immunocompromised patients are usually excluded from trials and guidelines on the management of ICU-acquired infections. The most common ICU-acquired infections in immunocompromised patients are ventilator-associated lower respiratory tract infections (which include ventilator-associated pneumonia and tracheobronchitis) and bloodstream infections. Recently, several large observational studies have shed light on some of the epidemiological specificities of these infections-as well as on the dynamics of colonization and infection with multidrug-resistant bacteria-in these patients, and these will be discussed in this review. Immunocompromised patients are also at higher risk than non-immunocompromised hosts of fungal and viral infections, and the diagnostic and therapeutic management of these infections will be covered. Finally, we will suggest some important areas of future investigation.
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Affiliation(s)
- Louis Kreitmann
- Department of Intensive Care Medicine, Imperial College Healthcare NHS Trust, London, UK
- Centre for Antimicrobial Optimisation, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, W12 0HS, UK
| | - Julie Helms
- Service de Médecine Intensive-Réanimation, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, 1, Place de l'Hôpital, 67091, Strasbourg Cedex, France
- ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Fédération Hospitalo-Universitaire (FHU) OMICARE, Université de Strasbourg (UNISTRA), Strasbourg, France
| | - Ignacio Martin-Loeches
- Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), Leinster, D08NYH1, Dublin, Ireland
- Pulmonary Intensive Care Unit, Respiratory Institute, Hospital Clinic of Barcelona, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), University of Barcelona, ICREA CIBERes, 08380, Barcelona, Spain
| | - Jorge Salluh
- D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Rio de Janeiro, RJ, 22281-100, Brazil
| | - Garyphallia Poulakou
- Third Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Sotiria General Hospital, Athens, Greece
| | - Frédéric Pène
- Médecine Intensive-Réanimation, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France
- Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Cité, Paris, France
| | - Saad Nseir
- Médecine Intensive-Réanimation, CHU de Lille, 59000, Lille, France.
- Inserm U1285, Université de Lille, CNRS, UMR 8576-UGSF, 59000, Lille, France.
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Perrotta F, Piscopiello D, Rizzo D, Iosa G, Garzya G, Calò P, Gemma D. Cytomegalovirus Pneumonia in a Patient with Down Syndrome. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:242. [PMID: 38399530 PMCID: PMC10890385 DOI: 10.3390/medicina60020242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 01/16/2024] [Accepted: 01/25/2024] [Indexed: 02/25/2024]
Abstract
Down syndrome (DS) is a chromosomal disorder due to the presence of an additional chromosome 21 that causes intellectual deficit and physical anomalies and predisposes patients to develop infections throughout their lives. Pneumonias are more serious in patients with DS, requiring hospitalization, and they represent an important cause of mortality in this population. Cytomegalovirus (CMV) causes widespread and serious infections in immunocompromised individuals, affecting the respiratory tract and, when causing interstitial pneumonia, associated with a high mortality rate. However, CMV-induced pneumonia is not reported in DS patients. The prevalence and severity of CMV respiratory infections in subjects with DS is unknown. This case describes a 50-year-old female patient with DS who developed extensive bilateral pneumonia with severe respiratory failure which required hospitalization in intensive care, intubation, and mechanical ventilation after approximately 10 days of empiric antibiotic and anitimycotic therapy for fever, cough, and dyspnea. The patient was diagnosed with CMV pneumonia and recovered after treatment with ganciclovir. To the best of our knowledge, this is the first reported case of CMV pneumonia in a patient with DS. This case aims to highlight that CMV pneumonia in individuals with DS can be a life-threatening condition. It also clarifies the importance of early diagnosis of infections from opportunistic pathogens such as CMV to ensure timely and efficient treatment.
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Affiliation(s)
- Francesco Perrotta
- Department of Anesthesia and Intensive Care, Azienda Ospedaliera Cardinale Panico, 73039 Tricase, Italy; (D.P.); (D.R.); (G.I.); (G.G.); (P.C.); (D.G.)
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9
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Zais IE, Sirotti A, Iesari S, Campioli E, Costantino A, Delbue S, Collini A, Guarneri A, Ambrogi F, Cacciola R, Ferraresso M, Favi E. Human cytomegalovirus-related gastrointestinal disease after kidney transplantation: A systematic review. Clin Transplant 2024; 38:e15218. [PMID: 38063324 DOI: 10.1111/ctr.15218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 11/14/2023] [Accepted: 11/27/2023] [Indexed: 01/31/2024]
Abstract
BACKGROUND Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients (KTRs). Signs and symptoms of the disease are extremely variable. Prompt anti-viral therapy administration and immunosuppression modification are key factors for optimizing management. However, complex work-up strategies are generally required to confirm the preliminary diagnosis. Unfortunately, solid evidence and guidelines on this specific topic are not available. We consequently aimed to summarize current knowledge on post-KT hCMV-related gastrointestinal disease (hCMV-GID). METHODS We conducted a systematic review (PROSPERO ID: CRD42023399363) about hCMV-GID in KTRs. RESULTS Our systematic review includes 52 case-reports and ten case-series, published between 1985 and 2022, collectively reporting 311 cases. The most frequently reported signs and symptoms of hCMV-GID were abdominal pain, diarrhea, epigastric pain, vomiting, fever, and GI bleeding. Esophagogastroduodenoscopy and colonoscopy were the primary diagnostic techniques. In most cases, the preliminary diagnosis was confirmed by histology. Information on anti-viral prophylaxis were extremely limited as much as data on induction or maintenance immunosuppression. Treatment included ganciclovir and/or valganciclovir administration. Immunosuppression modification mainly consisted of mycophenolate mofetil or calcineurin inhibitor minimization and withdrawal. In total, 21 deaths were recorded. Renal allograft-related outcomes were described for 26 patients only. Specifically, reported events were acute kidney injury (n = 17), transplant failure (n = 5), allograft rejection (n = 4), and irreversible allograft dysfunction (n = 3). CONCLUSIONS The development of local and national registries is strongly recommended to improve our understanding of hCMV-GID. Future clinical guidelines should consider the implementation of dedicated diagnostic and treatment strategies.
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Affiliation(s)
| | - Alessandro Sirotti
- General Surgery and Kidney Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Samuele Iesari
- General Surgery and Kidney Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Edoardo Campioli
- General Surgery and Kidney Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Andrea Costantino
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Serena Delbue
- Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy
| | - Andrea Collini
- Renal Transplant Unit, Siena University Hospital, Siena, Italy
| | - Andrea Guarneri
- Department of Clinical Sciences and Community Health (DISCCO), Università degli Studi di Milano, Milan, Italy
| | - Federico Ambrogi
- Department of Clinical Sciences and Community Health (DISCCO), Università degli Studi di Milano, Milan, Italy
| | - Roberto Cacciola
- Dipartimento di Scienze Chirurgiche, Università di Roma Tor Vergata, Rome, Italy
| | - Mariano Ferraresso
- General Surgery and Kidney Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health (DISCCO), Università degli Studi di Milano, Milan, Italy
| | - Evaldo Favi
- General Surgery and Kidney Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health (DISCCO), Università degli Studi di Milano, Milan, Italy
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10
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Lamps LW. Infectious Disease Pathology of the Gastrointestinal Tract: Diagnosing the Challenging Cases. Surg Pathol Clin 2023; 16:779-804. [PMID: 37863566 DOI: 10.1016/j.path.2023.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2023]
Abstract
Infectious diseases of the GI tract mimic a variety of other GI diseases, including chronic idiopathic inflammatory bowel disease and ischemia. It can be challenging to identify pathogens in tissue sections as well, as many trainees are not exposed to infectious disease pathology other than in the context of microbiology. Our ability to diagnose infections in formalin fixed, paraffin embedded material has grown exponentially with the advent of new histochemical and immunohistochemical stains, as well as more options for molecular testing. Correlating these diagnostic techniques with morphology has led to increasing understanding of the histologic patterns that are associated with specific pathogens.
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Affiliation(s)
- Laura W Lamps
- Department of Pathology, University of Michigan, NCRC Building 35, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
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11
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Windpessl M, Kostopoulou M, Conway R, Berke I, Bruchfeld A, Soler MJ, Sester M, Kronbichler A. Preventing infections in immunocompromised patients with kidney diseases: vaccines and antimicrobial prophylaxis. Nephrol Dial Transplant 2023; 38:ii40-ii49. [PMID: 37218705 DOI: 10.1093/ndt/gfad080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Indexed: 05/24/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic revealed that our understanding of infectious complications and strategies to mitigate severe infections in patients with glomerular diseases is limited. Beyond COVID-19, there are several infections that specifically impact care of patients receiving immunosuppressive measures. This review will provide an overview of six different infectious complications frequently encountered in patients with glomerular diseases, and will focus on recent achievements in terms of vaccine developments and understanding of the use of specific antimicrobial prophylaxis. These include influenza virus, Streptococcus pneumoniae, reactivation of a chronic or past infection with hepatitis B virus in cases receiving B-cell depletion, reactivation of cytomegalovirus, and cases of Pneumocystis jirovecii pneumonia in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Varicella zoster virus infections are particularly frequent in patients with systemic lupus erythematosus and an inactivated vaccine is available to use as an alternative to the attenuated vaccine in patients receiving immunosuppressants. As with COVID-19 vaccines, vaccine responses are generally impaired in older patients, and after recent administration of B-cell depleting agents, and high doses of mycophenolate mofetil and other immunosuppressants. Strategies to curb infectious complications are manifold and will be outlined in this review.
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Affiliation(s)
- Martin Windpessl
- Department of Internal Medicine IV, Nephrology, Klinikum Wels-Grieskirchen, Wels, Austria
| | | | - Richard Conway
- St James's Hospital, Dublin, Ireland
- Trinity College Dublin, Dublin, Ireland
| | - Ilay Berke
- Department of Nephrology, Marmara University School of Medicine, Istanbul, Turkey
| | - Annette Bruchfeld
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Department of Renal Medicine, Karolinska University Hospital and CLINTEC Karolinska Institutet, Stockholm, Sweden
| | - Maria Jose Soler
- Nephrology and Kidney Transplantation Research Group, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
- Nephrology Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Martina Sester
- Department of Transplant and Infection Immunology, Institute of Infection Medicine, Saarland University, Homburg, Germany
| | - Andreas Kronbichler
- Department of Medicine, University of Cambridge, Cambridge, UK
- Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK
- Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria
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12
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Mancuso J, Dalia T, Goyal A, Elliott DRF, Shah Z, Vidic A. Cytomegalovirus infection in heart transplant patient presenting as appendicitis. J Cardiol Cases 2023; 28:113-115. [PMID: 37671257 PMCID: PMC10477039 DOI: 10.1016/j.jccase.2023.04.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 03/30/2023] [Accepted: 04/23/2023] [Indexed: 09/07/2023] Open
Abstract
Cytomegalovirus (CMV) may manifest in various ways. While immunocompetent hosts may be asymptomatic or present with a mononucleosis-like illness, immunocompromised patients can have organ-specific disease capable of significant morbidity and mortality. CMV appendicitis is a particularly rare presentation. A 22-year-old female with a history of orthotopic heart transplantation presented to our hospital with a three-day history of worsening abdominal pain. A computed tomography scan of her abdomen was consistent with acute uncomplicated appendicitis, and she underwent laparoscopic appendectomy. Pathology revealed acute appendicitis with numerous large cells with intranuclear "owl's eye" inclusions characteristic of CMV. Her CMV viral load was elevated at 327,018 IU/ml. She was started on ganciclovir which resulted in improvement of her CMV level to 30,118 IU/ml within three weeks. CMV is a frequent cause of opportunistic infection in solid organ transplant patients and commonly involves the gastrointestinal tract. Acute appendicitis is a rarely reported complication to consider in the differential diagnosis of abdominal pain in immunocompromised patients. Learning objective Heart transplant recipients are at increased risk for opportunistic infections. Cytomegalovirus (CMV) is a frequent culprit and can present with a broad range of disease. A particularly rare presentation is that of acute appendicitis. We describe a case of a young woman with CMV appendicitis following orthotopic heart transplant.
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Affiliation(s)
- Joseph Mancuso
- Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Tarun Dalia
- Department of Cardiovascular Diseases, University of Kansas Medical Center, Kansas City, KS, USA
| | - Amandeep Goyal
- Department of Cardiovascular Diseases, University of Kansas Medical Center, Kansas City, KS, USA
| | | | - Zubair Shah
- Department of Cardiovascular Diseases, University of Kansas Medical Center, Kansas City, KS, USA
| | - Andrija Vidic
- Department of Cardiovascular Diseases, University of Kansas Medical Center, Kansas City, KS, USA
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13
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Babakhanlou R, Ravandi-Kashani F, Kontoyiannis DP. Neutropenic Enterocolitis: An Uncommon, but Fearsome Complication of Leukemia. J Hematol 2023; 12:59-65. [PMID: 37187499 PMCID: PMC10181327 DOI: 10.14740/jh1105] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 04/29/2023] [Indexed: 05/17/2023] Open
Abstract
Neutropenic enterocolitis (NEC) is a life-threatening condition occurring in severely neutropenic patients, following intensive chemotherapy for leukemia. Its pathogenesis is not entirely understood and believed to be multifactorial, including mucosal injury as a result of cytotoxic drugs, profound neutropenia, impaired host defense and possibly microbiota changes. Establishing an early diagnosis is key. The management of NEC remains undefined due to lack of high-quality clinical data. With a better understanding of the disease, a more conservative approach is preferred over surgical intervention. The involvement of a multi-disciplinary team, consisting of the oncologist, infectious diseases specialists and surgeons is highly recommended. This review aims to delineate insights into the pathophysiology and clinical presentation of NEC and to emphasize the diagnostic and therapeutic approach to this condition.
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Affiliation(s)
- Rodrick Babakhanlou
- Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA
- Corresponding Author: Rodrick Babakhanlou, Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
| | - Farhad Ravandi-Kashani
- Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Dimitrios P. Kontoyiannis
- Division of Internal Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA
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14
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Human cytomegalovirus: a survey of end-organ diseases and diagnostic challenges in solid organ transplant recipients. Curr Opin Organ Transplant 2022; 27:243-249. [PMID: 36354249 DOI: 10.1097/mot.0000000000000992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
PURPOSE OF REVIEW Human cytomegalovirus (CMV) infection is one of the most important infectious complications in solid organ transplant (SOT) recipients, leading to significant morbidity and mortality. Therefore, early detection and prompt treatment are imperative to improve transplant outcomes. This article highlights the clinical characteristics of the most common CMV end-organ diseases in SOT recipients and their diagnostic modalities and challenges. RECENT FINDINGS CMV can cause a variety of end-organ diseases in SOT recipients. Although CMV nucleic acid amplification by polymerase chain reaction (PCR) is frequently employed to detect CMV reactivation or infection, its predictive value for various CMV end-organ diseases remains uncertain. Given the limitation of PCR or other noninvasive tests, confirmation of CMV end-organ disease may require tissue biopsy, which may not be feasible or available, or may cause untoward complications. SUMMARY The utility of PCR to diagnose CMV end-organ disease is limited. As CMV can infect any organ system(s), clinicians caring for SOT recipients need to maintain vigilance for any signs and symptoms of end-organ disease to allow early recognition and prompt treatment. Invasive procedures might be needed to confirm the diagnosis and minimize the empirical use of antiviral therapy that may have substantial drug toxicities.
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15
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Kakiuchi T, Eguchi K, Koga D, Eguchi H, Nishi M, Sonoda M, Ishimura M, Matsuo M. Changes in bone marrow and peripheral blood lymphocyte subset findings with onset of hepatitis-associated aplastic anemia. Medicine (Baltimore) 2022; 101:e28953. [PMID: 35212305 PMCID: PMC8878616 DOI: 10.1097/md.0000000000028953] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 02/11/2022] [Indexed: 01/04/2023] Open
Abstract
RATIONALE Hepatitis-associated aplastic anemia (HAAA) is a rare illness that results in bone marrow failure following hepatitis development. The etiological agent remains unknown in most HAAA cases. However, clinical features of the disease and immunotherapy response indicate that immune-mediated factors play a central role in the pathogenesis of HAAA. Activation of cytotoxic T cells and increase in CD8 cells could exert cytotoxic effects on the myelopoietic cells in the bone marrow. PATIENT CONCERNS A 15-month-old boy was brought to our hospital with complaints of generalized petechiae and purpura observed a week prior to hospitalization. His liver was palpated 3 cm below the costal margin, platelet count was 0 × 104/μL, and alanine aminotransferase level was 1346 IU/L. A blood test indicated cytomegalovirus infection, and 3 bone marrow examinations revealed progressive HAAA. As the disease progressed to the 3rd, 6th, and 9th week after onset, CD4+ T cells were markedly decreased, CD8+ T cells were markedly increased, and the CD4/CD8 ratio was significantly decreased. The number of B cells and natural killer cells decreased with time, eventually reaching 0.0%. DIAGNOSIS HAAA. INTERVENTIONS Rabbit antithymocyte globulin and eltrombopag olamine (a thrombopoietin receptor agonist) were administered. OUTCOMES The patient's platelet count returned to normal, and bone marrow transplantation was avoided. The peripheral blood lymphocytes (PBLs) improved as the patient's general condition recovered. LESSONS This case demonstrates that HAAA induced by cytomegalovirus infection features decreasing CD4+ and increasing CD8+ PBLs as the bone marrow hypoplasia progresses. The PBLs return to their normal levels with the recovery from the disease. Our case findings thus support the involvement of immunological abnormality in HAAA.
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Affiliation(s)
- Toshihiko Kakiuchi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Katsuhide Eguchi
- Department of Pediatrics, Faculty of Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Daisuke Koga
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Hiroi Eguchi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Masanori Nishi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Motoshi Sonoda
- Department of Pediatrics, Faculty of Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Masataka Ishimura
- Department of Pediatrics, Faculty of Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Muneaki Matsuo
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
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16
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Godsell J, Chan S, Slade C, Bryant V, Douglass JA, Sasadeusz J, Yong MK. Cytomegalovirus in primary immunodeficiency. Curr Opin Infect Dis 2021; 34:663-671. [PMID: 34608876 DOI: 10.1097/qco.0000000000000797] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE OF REVIEW Cytomegalovirus (CMV) infection and disease are well described in the setting of secondary immunodeficiency. Less is known about CMV in the context of primary immunodeficiencies (PIDs), where inborn errors in one or more arms of the immune system result in variable degrees of CMV susceptibility. RECENT FINDINGS PID presents unique challenges in the diagnosis and management of CMV disease. The clinical presentation of CMV in PID is often severe, accelerated by underlying immune dysregulation and iatrogenic immunosuppression. Here we describe the clinical significance of CMV infection in PID, the key components of immune defence against CMV and how these are affected in specific PIDs. CMV disease is under-recognized as a complication of common variable immunodeficiency (CVID). High rates of CMV end-organ disease, mortality, development of CMV resistance and prolonged antiviral use have been observed in individuals with CVID. SUMMARY We recommend that clinicians tailor their approach to the individual based on their underlying immune deficit and maintain a high index of suspicion and low threshold for treatment. More research is required to improve stratification of CMV risk in PID, develop new diagnostic tools and manage end-organ disease in this cohort.
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Affiliation(s)
- Jack Godsell
- Department of Clinical Immunology & Allergy, Royal Melbourne Hospital
| | - Samantha Chan
- Department of Clinical Immunology & Allergy, Royal Melbourne Hospital
- Immunology Division, Walter & Eliza Hall Institute of Medical Research
- Department of Medicine, University of Melbourne
| | - Charlotte Slade
- Department of Clinical Immunology & Allergy, Royal Melbourne Hospital
- Immunology Division, Walter & Eliza Hall Institute of Medical Research
| | - Vanessa Bryant
- Department of Clinical Immunology & Allergy, Royal Melbourne Hospital
- Immunology Division, Walter & Eliza Hall Institute of Medical Research
| | - Jo Anne Douglass
- Department of Clinical Immunology & Allergy, Royal Melbourne Hospital
- Department of Medicine, University of Melbourne
| | - Joe Sasadeusz
- Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne
| | - Michelle K Yong
- Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville
- National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
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17
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Karaba AH, Figueroa A, Werbel WA, Dioverti MV, Steinke SM, Ray SC, Cox AL, Avery RK. Interleukin-18 and tumor necrosis factor-α are elevated in solid organ transplant recipients with possible cytomegalovirus end-organ disease. Transpl Infect Dis 2021; 23:e13682. [PMID: 34216086 PMCID: PMC8455421 DOI: 10.1111/tid.13682] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 06/17/2021] [Accepted: 06/21/2021] [Indexed: 12/14/2022]
Abstract
End-organ cytomegalovirus (CMV) disease can be life threatening to solid organ transplant recipients. Diagnosis is often complicated by variation in amount of CMV DNA in plasma and the need for an invasive procedure to obtain a biopsy of the suspected affected organ, which can delay recognition and treatment. Several inflammatory cytokines are elevated in CMV disease, and the purpose of this study was to determine if they could be used to distinguish solid organ transplant recipients with CMV DNAemia alone from those with possible end-organ CMV disease. We found that regardless of pre-transplant CMV serostatus, plasma interleukin (IL)-18, tumor necrosis factor-α (TNF-α), and amount of CMV DNA in plasma were increased in possible end-organ CMV disease, with elevated IL-18 associated with increased odds of possible end-organ CMV disease even after adjusting for amount of CMV DNA. These findings highlight IL-18 and TNF-α as potential non-invasive markers of possible end-organ CMV disease regardless of transplanted organ or serostatus in solid organ transplant recipients.
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Affiliation(s)
- Andrew H. Karaba
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Alexis Figueroa
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - William A. Werbel
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Maria Veronica Dioverti
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Seema Mehta Steinke
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Stuart C. Ray
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Andrea L. Cox
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
- Bloomberg Kimmel Institute for Cancer Immunotherapy Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Robin K. Avery
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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18
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Craviotto V, Furfaro F, Loy L, Zilli A, Peyrin-Biroulet L, Fiorino G, Danese S, Allocca M. Viral infections in inflammatory bowel disease: Tips and tricks for correct management. World J Gastroenterol 2021; 27:4276-4297. [PMID: 34366605 PMCID: PMC8316900 DOI: 10.3748/wjg.v27.i27.4276] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/01/2021] [Accepted: 05/15/2021] [Indexed: 02/06/2023] Open
Abstract
Over the past decades, the treatment of inflammatory bowel diseases (IBD) has become more targeted, anticipating the use of immune-modifying therapies at an earlier stage. This top-down approach has been correlated with favorable short and long-term outcomes, but it has also brought with it concerns regarding potential infectious complications. This large IBD population treated with immune-modifying therapies, especially if combined, has an increased risk of severe infections, including opportunistic infections that are sustained by viral, bacterial, parasitic, and fungal agents. Viral infections have emerged as a focal safety concern in patients with IBD, representing a challenge for the clinician: they are often difficult to diagnose and are associated with significant morbidity and mortality. The first step is to improve effective preventive strategies, such as applying vaccination protocols, adopt adequate prophylaxis and educate patients about potential risk factors. Since viral infections in immunosuppressed patients may present atypical signs and symptoms, the challenges for the gastroenterologist are to suspect, recognize and diagnose such complications. Appropriate treatment of common viral infections allows us to minimize their impact on disease outcomes and patients’ lives. This practical review supports this standard of care to improve knowledge in this subject area.
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Affiliation(s)
- Vincenzo Craviotto
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
| | - Federica Furfaro
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
| | - Laura Loy
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
| | - Alessandra Zilli
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
| | - Laurent Peyrin-Biroulet
- Department of Hepato-Gastroenterology and Inserm U954, University Hospital of Nancy, Lorraine University, Nancy 54511, France
| | - Gionata Fiorino
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milano, Italy
| | - Silvio Danese
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milano, Italy
| | - Mariangela Allocca
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milano, Italy
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19
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Taksinwarajarn T, Sobhonslidsuk A, Kantachuvesiri S, Thongprayoon C, Cheungpasitporn W, Bruminhent J. Role of highly sensitive nucleic acid amplification testing for plasma cytomegalovirus DNA load in diagnosis of cytomegalovirus gastrointestinal disease among kidney transplant recipients. Transpl Infect Dis 2021; 23:e13635. [PMID: 33982825 DOI: 10.1111/tid.13635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 05/02/2021] [Accepted: 05/06/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND High plasma cytomegalovirus (CMV) DNA load is generally associated with CMV tissue-invasive disease in solid organ transplant recipients. However, some tissue-invasive diseases, especially CMV gastrointestinal (GI) disease, have undetectable to very low plasma CMV DNA loads. Highly sensitive nucleic acid amplification testing (NAAT) has been increasingly used to quantify low-level CMV DNA loads. Our primary objective was to investigate the epidemiology of CMV GI disease and evaluate the validity of plasma CMV NAAT for the diagnosis of CMV GI disease in kidney transplant (KT) recipients. METHODS We conducted a retrospective study of all KT recipients who developed CMV GI disease from January 2016 to December 2018. Plasma CMV DNA load was measured using real-time PCR. The cut-off value of plasma CMV DNA load for diagnosing and risk factors of CMV GI disease were analyzed. RESULTS A total 17 (3.4%) cases of CMV GI disease occurred in 494 KT recipients. Fifteen (88%) patients had CMV D + /R + serostatus. Fourteen (82%) patients developed CMV GI disease within 6 months after KT. Plasma CMV DNA loads were detectable in all (100%) patients with a median load 11,102 (IQR 2,935-107,160) IU/ml. A plasma CMV DNA load of 4,063 IU/ml was established as al cut-off for diagnosing CMV GI disease (AUC 0.74, sensitivity 76.5%, specificity 70%, PPV 68, NPV 78). In multivariate analysis, prolonged cold ischemic time (HR 1.14, 95% CI 1.05-1.23, P = .002) and CMV D + /R - serostatus (HR 9.31, 95% CI 2.12-40.74, P = .003) were associated with CMV GI disease. CONCLUSIONS Using highly sensitive NAAT could potentially assist in the diagnosis of CMV GI disease in a CMV D + /R + serostatus setting. KT recipients with CMV seromismatch and prolonged cold ischemic time are at higher risk of CMV GI disease.
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Affiliation(s)
- Touchapong Taksinwarajarn
- Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Abhasnee Sobhonslidsuk
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.,Excellence Center for Organ Transplantation, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Surasak Kantachuvesiri
- Excellence Center for Organ Transplantation, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.,Division of Nephrology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Charat Thongprayoon
- Division of Nephrology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Wisit Cheungpasitporn
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
| | - Jackrapong Bruminhent
- Excellence Center for Organ Transplantation, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.,Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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20
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Chaudhuri A, Goddard EA, Green M, Ardura MI. Diarrhea in the pediatric solid organ transplantation recipient: A multidisciplinary approach to diagnosis and management. Pediatr Transplant 2021; 25:e13886. [PMID: 33142366 DOI: 10.1111/petr.13886] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 07/25/2020] [Accepted: 09/09/2020] [Indexed: 12/11/2022]
Abstract
Diarrhea in the pediatric solid organ transplantation (SOT) recipient is a frequent complaint that is associated with significant morbidity and impaired quality of life. There are limited published data regarding the specific epidemiology, diagnostic evaluation, and treatment of diarrhea after SOT in children. Pediatric SOT recipients have an increased risk of developing diarrhea because of a generalized immunosuppressed state, epidemiologic exposures, and polypharmacy. There is a need to standardize the diagnostic evaluation of diarrhea in children after SOT to facilitate an accurate diagnosis and timely treatment. Herein, we review the available published data and propose a systematic, stepwise approach to the evaluation of diarrhea in this high-risk population, focusing on timely diagnosis of both infectious and non-infectious causes, in order to provide focused management. Prospective studies are needed to better assess the true prevalence, risk factors for, etiologies, and complications of diarrhea in pediatric SOT patients that will guide optimal management. Development of effective vaccines and antiviral therapies for enteric viruses may also contribute to improved outcomes.
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Affiliation(s)
- Abanti Chaudhuri
- Department of Pediatrics, Division of Nephrology, Stanford University, Stanford, CA, USA
| | - Elizabeth Anne Goddard
- Department of Pediatrics, Division of Pediatric Gastroenterology, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa
| | - Michael Green
- Department of Pediatrics, Division of Infectious Diseases, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - Monica I Ardura
- Department of Pediatrics, Division of Infectious Diseases & Host Defense Program, Nationwide Children's Hospital & The Ohio State University, Columbus, OH, USA
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21
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Singh P, Bentall AJ, Langstraat CL, Swanson AA, Deziel PJ, Huang Y, Razonable RR. A rare manifestation of CMV disease in a kidney transplant recipient. Transpl Infect Dis 2021; 23:e13527. [PMID: 33237608 DOI: 10.1111/tid.13527] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 11/03/2020] [Accepted: 11/11/2020] [Indexed: 11/28/2022]
Affiliation(s)
- Prince Singh
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Andrew J Bentall
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | | | - Amy A Swanson
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA
| | - Paul J Deziel
- Division of Infectious Diseases, Mayo Clinic, Rochester, MN, USA
| | - Yajue Huang
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA
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22
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Razonable RR, Inoue N, Pinninti SG, Boppana SB, Lazzarotto T, Gabrielli L, Simonazzi G, Pellett PE, Schmid DS. Clinical Diagnostic Testing for Human Cytomegalovirus Infections. J Infect Dis 2021; 221:S74-S85. [PMID: 32134488 DOI: 10.1093/infdis/jiz601] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Human cytomegalovirus (HCMV) infections are among the most common complications arising in transplant patients, elevating the risk of various complications including loss of graft and death. HCMV infections are also responsible for more congenital infections worldwide than any other agent. Congenital HCMV (cCMV) infections are the leading nongenetic cause of sensorineural hearing loss and a source of significant neurological disabilities in children. While there is overlap in the clinical and laboratory approaches to diagnosis of HCMV infections in these settings, the management, follow-up, treatment, and diagnostic strategies differ considerably. As yet, no country has implemented a universal screening program for cCMV. Here, we summarize the issues, limitations, and application of diagnostic strategies for transplant recipients and congenital infection, including examples of screening programs for congenital HCMV that have been implemented at several centers in Japan, Italy, and the United States.
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Affiliation(s)
- Raymund R Razonable
- Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.,William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Swetha G Pinninti
- Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Suresh B Boppana
- Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.,Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Tiziana Lazzarotto
- Operative Unit of Microbiology and Virology, Department of Specialized, Experimental, and Diagnostic Medicine, Polyclinic of St Orsola-Malpighi, University of Bologna, Italy
| | - Liliana Gabrielli
- Operative Unit of Microbiology and Virology, Department of Specialized, Experimental, and Diagnostic Medicine, Polyclinic of St Orsola-Malpighi, University of Bologna, Italy
| | - Giuliana Simonazzi
- Operative Unit of Obstetrics and Prenatal Medicine, Department of Medical Surgical Sciences, Polyclinic of St Orsola-Malpighi, University of Bologna, Italy
| | - Philip E Pellett
- Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, Michigan, USA
| | - D Scott Schmid
- Viral Vaccine Preventable Diseases Branch, Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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23
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Gioco R, Puzzo L, Patanè M, Corona D, Trama G, Veroux P, Veroux M. Post-transplant colitis after kidney transplantation: clinical, endoscopic and histological features. Aging (Albany NY) 2020; 12:24709-24720. [PMID: 33353887 PMCID: PMC7803550 DOI: 10.18632/aging.202345] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 11/16/2020] [Indexed: 12/19/2022]
Abstract
Chronic immunosuppression may increase the risk of post-transplant infection and medication-related injury and may also be responsible for the increased risk of gastrointestinal complications in kidney transplant recipients. Differentiating the various forms of post-transplant colitis is challenging, since most have similar clinical and histological features. This study evaluated the incidence of post-transplant gastrointestinal complications during screening colonoscopy. Kidney transplant recipients undergoing a colonoscopy for any reasons in the period 2014-2018 were included. Among the 134 patients completing the colonoscopy, 74 patients (56%) had an abnormal finding: an adenoma was found in 25 patients (18.6%), while 19 patients (14.1%) had colitis. Mycophenolic acid/related colitis was the most common colitis (6%), while 7 patients (5.2%) developed a de novo inflammatory bowel disease. Patients with post-transplant colitis were younger and with shorter time from transplant compared to patients without colitis. In conclusions, immunosuppression may predispose kidney transplant recipients to an increased risk of post-transplant colitis. Diagnostic colonoscopy should be encouraged in all transplant patients with refractory diarrhea and gastrointestinal symptoms to allow a prompt diagnosis and a timely treatment, finally improving the quality of life and long-term outcomes of affected patients.
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Affiliation(s)
- Rossella Gioco
- General Surgery Unit, University Hospital of Catania, Catania 95123, Italy
| | - Lidia Puzzo
- Pathology Unit, Department of Medical and Surgical Sciences and Advanced Technologies, University of Catania, Catania 95123, Italy
| | - Marco Patanè
- Organ Transplant Unit, University Hospital of Catania, Catania 95123, Italy
| | - Daniela Corona
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95123, Italy
| | - Giuseppe Trama
- Gastroenterology Unit, University Hospital of Catania, Catania 95123, Italy
| | | | - Massimiliano Veroux
- General Surgery Unit, University Hospital of Catania, Catania 95123, Italy.,Organ Transplant Unit, University Hospital of Catania, Catania 95123, Italy
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24
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Limaye AP, Babu TM, Boeckh M. Progress and Challenges in the Prevention, Diagnosis, and Management of Cytomegalovirus Infection in Transplantation. Clin Microbiol Rev 2020; 34:34/1/e00043-19. [PMID: 33115722 PMCID: PMC7920732 DOI: 10.1128/cmr.00043-19] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hosts with compromised or naive immune systems, such as individuals living with HIV/AIDS, transplant recipients, and fetuses, are at the highest risk for complications from cytomegalovirus (CMV) infection. Despite substantial progress in prevention, diagnostics, and treatment, CMV continues to negatively impact both solid-organ transplant (SOT) and hematologic cell transplant (HCT) recipients. In this article, we summarize important developments in the field over the past 10 years and highlight new approaches and remaining challenges to the optimal control of CMV infection and disease in transplant settings.
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Affiliation(s)
- Ajit P Limaye
- Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA
| | - Tara M Babu
- Division of Infectious Diseases, University of Rochester Medical Center, Rochester, New York, USA
- Department of Infectious Diseases, Overlake Medical Center, Bellevue, Washington, USA
| | - Michael Boeckh
- Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
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25
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Gioco R, Corona D, Ekser B, Puzzo L, Inserra G, Pinto F, Schipa C, Privitera F, Veroux P, Veroux M. Gastrointestinal complications after kidney transplantation. World J Gastroenterol 2020; 26:5797-5811. [PMID: 33132635 PMCID: PMC7579754 DOI: 10.3748/wjg.v26.i38.5797] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 05/28/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal complications are common after renal transplantation, and they have a wide clinical spectrum, varying from diarrhoea to post-transplant inflammatory bowel disease (IBD). Chronic immunosuppression may increase the risk of post-transplant infection and medication-related injury and may also be responsible for IBD in kidney transplant re-cipients despite immunosuppression. Differentiating the various forms of post-transplant colitis is challenging, since most have similar clinical and histological features. Drug-related colitis are the most frequently encountered colitis after kidney transplantation, particularly those related to the chronic use of mycophenolate mofetil, while de novo IBDs are quite rare. This review will explore colitis after kidney transplantation, with a particular focus on different clinical and histological features, attempting to clearly identify the right treatment, thereby improving the final outcome of patients.
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Affiliation(s)
- Rossella Gioco
- General Surgery Unit, University Hospital of Catania, Catania 95123, Italy
| | - Daniela Corona
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95123, Italy
| | - Burcin Ekser
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, United States
| | - Lidia Puzzo
- Pathology Unit, Department of Medical and Surgical Sciences and Advanced Technologies, University of Catania, Catania 95123, Italy
| | - Gaetano Inserra
- Gastroenterology Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania 95100, Italy
| | - Flavia Pinto
- General Surgery Unit, University Hospital of Catania, Catania 95123, Italy
| | - Chiara Schipa
- General Surgery Unit, University Hospital of Catania, Catania 95123, Italy
| | | | | | - Massimiliano Veroux
- General Surgery Unit, Organ Transplant Unit, University Hospital of Catania, Catania 95123, Italy
- Department of Medical and Surgical Sciences and Advanced Technologies, University Hospital of Catania, Catania 95123, Italy
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26
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Colon perforation due to cytomegalovirus infection in a patient with idiopathic hypereosinophilic syndrome: a case report. BMC Gastroenterol 2020; 20:238. [PMID: 32703162 PMCID: PMC7376729 DOI: 10.1186/s12876-020-01381-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 07/13/2020] [Indexed: 11/26/2022] Open
Abstract
Background Hypereosinophilic syndrome (HES) is a very rare disease and usually treated with corticosteroids. Gastrointestinal (GI) cytomegalovirus (CMV) infection is also rare but frequent in patients with immunocompromised status. These two related diseases present with similar manifestations, and may result in a life-threatening complication: perforation. However, the treatment strategies differ greatly. Here, we report a case of colon perforation due to cytomegalovirus infection in a patient with idiopathic HES. Case presentation A 41-year-old man with a history of HES was transferred to our hospital due to an acute onset of abdominal pain. During the treatment course of HES, this patient received CMV-DNA test with a result of < 2000 copies/ml. Computed tomography (CT) suggested colon perforation. An emergency surgery was performed immediately. Pathological diagnosis revealed CMV infection and infiltration of eosinophils. This patient received both anti-CMV therapy and immunosuppression therapy. Subsequently, the patient recovered and was discharged 25 days after the operation. Conclusion During the course of HES treatment, CMV infection should be reconsidered if digestive symptoms relapse.
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Natori Y, Alghamdi A, Tazari M, Miller V, Husain S, Komatsu T, Griffiths P, Ljungman P, Orchanian-Cheff A, Kumar D, Humar A, Alexander B, Avery R, Baldanti F, Barnett S, Baum P, Berrey MM, Birnkrant D, Blumberg E, Boeckh M, Boutolleau D, Bowlin T, Brooks J, Chemaly R, Chou S, Cloherty G, Cruikshank W, Dropulic L, Einsele H, Erdman J, Fahle G, Fallon L, Gillis H, Gonzalez D, Griffiths P, Gunter K, Hirsch H, Hodowanec A, Humar A, Hunt P, Josephson F, Komatsu T, Kotton C, Krause P, Kuhr F, Lademacher C, Lanier R, Lazarus T, Leake J, Leavitt R, Lehrman SN, Li L, Ljungman P, Lodding PI, Lundgren J, Martinez-Murillo F(P, Mayer H, McCutcheon M, McKinnon J, Mertens T, Miller V, Modarress K, Mols J, Mossman S, Murata Y, Murawski D, Murray J, Natori Y, Nichols G, O’Rear J, Peggs K, Pikis A, Prichard M, Razonable R, Riches M, Roberts J, Saber W, Sayada C, Singer M, Stamminger T, Wijatyk A, Yu D, Zeiher B. Use of Viral Load as a Surrogate Marker in Clinical Studies of Cytomegalovirus in Solid Organ Transplantation: A Systematic Review and Meta-analysis. Clin Infect Dis 2019; 66:617-631. [PMID: 29020339 DOI: 10.1093/cid/cix793] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 09/01/2017] [Indexed: 12/22/2022] Open
Abstract
Symptomatic cytomegalovirus (CMV) disease has been the standard endpoint for clinical trials in organ transplant recipients. Viral load may be a more relevant endpoint due to low frequency of disease. We performed a meta-analysis and systematic review of the literature. We found several lines of evidence to support the validity of viral load as an appropriate surrogate end-point, including the following: (1) viral loads in CMV disease are significantly greater than in asymptomatic viremia (odds ratio, 9.3 95% confidence interval, 4.6-19.3); (2) kinetics of viral replication are strongly associated with progression to disease; (3) pooled incidence of CMV viremia and disease is significantly lower during prophylaxis compared with the full patient follow-up period (viremia incidence: 3.2% vs 34.3%; P < .001) (disease incidence: 1.1% vs 13.0%; P < .001); (4) treatment of viremia prevented disease; and (5) viral load decline correlated with symptom resolution. Based on the analysis, we conclude that CMV load is an appropriate surrogate endpoint for CMV trials in organ transplant recipients.
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Affiliation(s)
- Yoichiro Natori
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Ali Alghamdi
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.,King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
| | - Mahmood Tazari
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Veronica Miller
- Forum for Collaborative Research, University of California, Berkeley
| | - Shahid Husain
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Takashi Komatsu
- Division of Antiviral Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland
| | - Paul Griffiths
- Institute for Immunity and Transplantation, University College London Medical School, United Kingdom
| | - Per Ljungman
- Division of Hematology, Department of Medicine Huddigne, Karolinksa Institutet, Stockholm, Sweden
| | - Ani Orchanian-Cheff
- Library and Information Services, University Health Network, Toronto, Ontario, Canada
| | - Deepali Kumar
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Atul Humar
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
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Krummenacher M, Banovic T, Kette F, Smith W, Hissaria P. Drug reaction with eosinophilia and systemic symptoms and cytomegalovirus colitis. Ann Allergy Asthma Immunol 2019; 123:401-403. [PMID: 31376489 DOI: 10.1016/j.anai.2019.07.024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 07/16/2019] [Accepted: 07/24/2019] [Indexed: 12/20/2022]
Affiliation(s)
| | - Tatjana Banovic
- SA Pathology, Royal Adelaide Hospital, Adelaide, South Australia
| | - Frank Kette
- Royal Adelaide Hospital, Adelaide, South Australia
| | | | - Pravin Hissaria
- SA Pathology, Royal Adelaide Hospital, Adelaide, South Australia
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Yokose T, Obara H, Shinoda M, Nakano Y, Kitago M, Yagi H, Abe Y, Yamada Y, Matsubara K, Oshima G, Hori S, Ibuki S, Higashi H, Masuda Y, Hayashi M, Mori T, Kawaida M, Fujimura T, Hoshino K, Kameyama K, Kuroda T, Kitagawa Y. Colon perforation due to antigenemia-negative cytomegalovirus gastroenteritis after liver transplantation: A case report and review of literature. World J Gastroenterol 2019; 25:1899-1906. [PMID: 31057303 PMCID: PMC6478612 DOI: 10.3748/wjg.v25.i15.1899] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 03/03/2019] [Accepted: 03/16/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) remains a critical complication after solid-organ transplantation. The CMV antigenemia (AG) test is useful for monitoring CMV infection. Although the AG-positivity rate in CMV gastroenteritis is known to be low at onset, almost all cases become positive during the disease course. We treated a patient with transverse colon perforation due to AG-negative CMV gastroenteritis, following a living donor liver transplantation (LDLT).
CASE SUMMARY The patient was a 52-year-old woman with decompensated liver cirrhosis as a result of autoimmune hepatitis who underwent a blood-type compatible LDLT with her second son as the donor. On day 20 after surgery, upper and lower gastrointestinal endoscopy (GE) revealed multiple gastric ulcers and transverse colon ulcers. The biopsy tissue immunostaining confirmed a diagnosis of CMV gastroenteritis. On day 28 after surgery, an abdominal computed tomography revealed transverse colon perforation, and simple lavage and drainage were performed along with an urgent ileostomy. Although the repeated remission and aggravation of CMV gastroenteritis and acute cellular rejection made the control of immunosuppression difficult, the upper GE eventually revealed an improvement in the gastric ulcers, and the biopsy samples were negative for CMV. The CMV-AG test remained negative, therefore, we had to evaluate the status of the CMV infection on the basis of the clinical symptoms and GE.
CONCLUSION This case report suggests a monitoring method that could be useful for AG-negative CMV gastroenteritis after a solid-organ transplantation.
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Affiliation(s)
- Takahiro Yokose
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Hideaki Obara
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Masahiro Shinoda
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Yutaka Nakano
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Hiroshi Yagi
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Yuta Abe
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Yohei Yamada
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Kentaro Matsubara
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Go Oshima
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Shutaro Hori
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Sho Ibuki
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Hisanobu Higashi
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Yuki Masuda
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Masanori Hayashi
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Takehiko Mori
- Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Miho Kawaida
- Department of Pathology, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Takumi Fujimura
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Ken Hoshino
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Kaori Kameyama
- Department of Pathology, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Tatsuo Kuroda
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
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30
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Razonable RR, Humar A. Cytomegalovirus in solid organ transplant recipients-Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33:e13512. [PMID: 30817026 DOI: 10.1111/ctr.13512] [Citation(s) in RCA: 460] [Impact Index Per Article: 76.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Accepted: 02/11/2019] [Indexed: 12/11/2022]
Abstract
Cytomegalovirus (CMV) is one of the most common opportunistic infections that affect the outcome of solid organ transplantation. This updated guideline from the American Society of Transplantation Infectious Diseases Community of Practice provides evidence-based and expert recommendations for screening, diagnosis, prevention, and treatment of CMV in solid organ transplant recipients. CMV serology to detect immunoglobulin G remains as the standard method for pretransplant screening of donors and transplant candidates. Antiviral prophylaxis and preemptive therapy are the mainstays of CMV prevention. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is highlighted, as a result of variability of CMV nucleic acid testing, even in the contemporary era when calibrators are standardized. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management. Strategies for managing drug-resistant CMV infection are presented. There is an increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, but their role in optimizing CMV prevention and treatment efforts has yet to be demonstrated. Specific issues related to pediatric transplant recipients are discussed.
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Affiliation(s)
| | - Atul Humar
- University Health Network, Toronto, Ontario, Canada.,Transplant Institute, University of Toronto, Toronto, Ontario, Canada
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31
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Abstract
PURPOSE OF REVIEW Cytomegalovirus (CMV) colitis is a relatively common end-organ infectious complication in immunocompromised hosts which negatively affects clinical outcomes. This paper presents the contemporary approaches to the diagnosis and management of CMV colitis and discusses some of the controversies of this condition, focusing on methods of diagnosis. RECENT FINDINGS While certain risk factors for CMV colitis are well recognized, the clinical as well as endoscopic features of this condition are nonspecific. Rapid diagnosis and management are usually needed, especially in critically ill patients, which necessitate invasive diagnostic procedures. Hematoxylin and eosin staining of colonic mucosal tissue may show the typical viral inclusions associated with CMV colitis that are highly specific for this condition. However, the staining has low sensitivity compared to immunohistochemistry, which is considered the gold standard for diagnosis of CMV colitis. Tissue polymerase chain reaction (PCR) is highly sensitive for diagnosis, but is controversial for many reasons, detailed in this paper. A high index of suspicion is needed, and once diagnosis is made, treatment should be highly considered to improve the outcome of these severely ill patients. Noninvasive diagnostic tests will be available in the future and will hopefully improve the diagnosis and care of patients with CMV colitis.
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Affiliation(s)
- Anat Yerushalmy-Feler
- Pediatric Gastroenterology Unit, Pediatrics Department, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center, 6 Weizman Street, 6423906, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - Shlomi Cohen
- Pediatric Gastroenterology Unit, Pediatrics Department, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center, 6 Weizman Street, 6423906, Tel Aviv, Israel. .,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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32
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Kredel LI, Mundt P, van Riesen L, Jöhrens K, Hofmann J, Loddenkemper C, Siegmund B, Preiß JC. Accuracy of diagnostic tests and a new algorithm for diagnosing cytomegalovirus colitis in inflammatory bowel diseases: a diagnostic study. Int J Colorectal Dis 2019; 34:229-237. [PMID: 30276706 DOI: 10.1007/s00384-018-3170-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/25/2018] [Indexed: 02/04/2023]
Abstract
PURPOSE The optimal method for detecting CMV colitis in patients with inflammatory bowel disease (IBD) has not been established. We wanted to investigate which diagnostic test would be most accurate when defining CMV colitis rather by the further clinical course than by using another diagnostic modality. METHODS All consecutive patients with moderately or severely active IBD who had been tested for CMV by PCR, histology, or antigenemia assay at the two campuses CBF and CCM of the Charité - Universitätsmedizin Berlin between September 2006 and September 2009 were included in this retrospective study. During that time, in patients with a positive CMV test, immunosuppressive treatment of any kind was immediately reduced and antiviral treatment was started. This allowed identifying patients who responded to antiviral treatment and those who only responded to later escalation of immunosuppressive therapy. RESULTS One hundred and nine patients were identified, out of whom nine were considered to have clinically relevant CMV colitis. Sensitivity and specificity were 1 and 0.94 for CMV PCR and 0.5 and 1 for pp65 antigen immunofluorescence assay from peripheral blood, 0.67 and 0.98 for immunohistochemistry, and 0.17 and 0.98 for hematoxylin-eosin staining. When using absence of leukocytosis, splenomegaly, and steroid refractory disease as clinical parameters to test for CMV colitis, blood CMV PCR and immunohistochemistry were able to exclude CMV colitis in negative patients with a 75% likelihood of positive patients to have clinically relevant CMV colitis. CONCLUSIONS Blood-based CMV PCR together with simple clinical parameters can exclude clinically relevant CMV colitis at a high specificity.
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Affiliation(s)
- Lea I Kredel
- Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Pamela Mundt
- Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203, Berlin, Germany
- Praxis Jessen + Kollegen, Akademische Lehrpraxis der Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Linda van Riesen
- Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203, Berlin, Germany
- Klinik für Innere Medizin - Schwerpunkt Gastroenterologie, DRK Kliniken Westend, Berlin, Germany
| | - Korinna Jöhrens
- Institut für Pathologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Jörg Hofmann
- Institut für Virologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | | | - Britta Siegmund
- Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Jan C Preiß
- Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203, Berlin, Germany.
- Klinik für Innere Medizin - Gastroenterologie, Diabetologie und Hepatologie, Vivantes Klinikum Neukölln, Berlin, Germany.
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33
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The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation 2019; 102:900-931. [PMID: 29596116 DOI: 10.1097/tp.0000000000002191] [Citation(s) in RCA: 807] [Impact Index Per Article: 134.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Despite recent advances, cytomegalovirus (CMV) infections remain one of the most common complications affecting solid organ transplant recipients, conveying higher risks of complications, graft loss, morbidity, and mortality. Research in the field and development of prior consensus guidelines supported by The Transplantation Society has allowed a more standardized approach to CMV management. An international multidisciplinary panel of experts was convened to expand and revise evidence and expert opinion-based consensus guidelines on CMV management including prevention, treatment, diagnostics, immunology, drug resistance, and pediatric issues. Highlights include advances in molecular and immunologic diagnostics, improved understanding of diagnostic thresholds, optimized methods of prevention, advances in the use of novel antiviral therapies and certain immunosuppressive agents, and more savvy approaches to treatment resistant/refractory disease. The following report summarizes the updated recommendations.
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Real-time quantitative PCR analysis of endoscopic biopsies for diagnosing CMV gastrointestinal disease in non-HIV immunocompromised patients: a diagnostic accuracy study. Eur J Clin Microbiol Infect Dis 2018; 37:2389-2396. [PMID: 30255430 DOI: 10.1007/s10096-018-3387-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 09/19/2018] [Indexed: 12/27/2022]
Abstract
Cytomegalovirus gastrointestinal diseases (CMV-GIDs) are end-organ diseases of the gastrointestinal (GI) tract caused by CMV in immunocompromised patients. We aimed to evaluate the performance of quantitative polymerase chain reaction (qPCR) on endoscopic biopsies. We retrospectively reviewed the qPCR data on endoscopic biopsies in nonhuman immunodeficiency virus (HIV) immunocompromised patients between January 2009 and May 2015. The performance of the qPCR for CMV-GID was evaluated with the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). A total of 195 patients were included, and 28 patients with confirmed CMV-GID were identified. The AUROC of the qPCR was 0.935 (95% confidence interval [CI], 0.885 to 0.985), the sensitivity was 89.3% (95% CI, 71.8 to 97.7%), and the specificity was 85.6% (95% CI, 79.4 to 97.6%) with a cutoff value of 180 copies/μg DNA. The proportion of patients with inflammatory bowel disease in the histopathology-negative, PCR-positive group was smaller than that in the histopathology-positive group (10.7 vs 35.0%, p = 0.026), but other characteristics were not significantly different. The use of qPCR on endoscopic biopsies demonstrated good diagnostic performance for detecting CMV in non-HIV immunocompromised patients. It may increase the diagnostic yield when combined with a conventional histopathology.
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Zavrelova A, Radocha J, Pliskova L, Paterova P, Vejrazkova E, Cyrany J, Gabalec F, Podhola M, Zak P. Detection of cytomegalovirus DNA in fecal samples in the diagnosis of enterocolitis after allogeneic stem cell transplantation. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2018; 162:227-231. [PMID: 29765165 DOI: 10.5507/bp.2018.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 04/17/2018] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Cytomegalovirus enterocolitis is a rare but potentially life threatening complication after allogeneic stem cell transplantation. Its early diagnosis and treatment are essential for a successful outcome. OBJECTIVE To determine the potential benefit of fecal CMV DNA detection in the diagnosis of CMV colitis among stem cell transplant recipients. STUDY DESIGN Biopsies from the lower gastrointestinal tract, taken during 69 episodes of diarrhea, were compared with fecal samples previously examined for CMV DNA in 45 patients after allogeneic stem cell transplantation. RESULTS Six confirmed cases of CMV colitis were observed, with 16 out of 69 (23%) fecal samples proving positive for CMV DNA. Only one positive sample correlated with histologically confirmed CMV colitis, and 15 samples were evaluated as false positive. These results provide a 16.7% sensitivity and 76.2% specificity in the diagnosis of CMV enterocolitis. CONCLUSION The examination of fecal samples for the presence of CMV DNA has very low potential in the diagnosis of CMV enterocolitis after allogeneic stem cell transplantation; therefore, a biopsy of the gastrointestinal mucosa is still warranted for correct diagnosis.
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Affiliation(s)
- Alzbeta Zavrelova
- 4 th Department of Internal Medicine - Hematology, University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Jakub Radocha
- 4 th Department of Internal Medicine - Hematology, University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Lenka Pliskova
- Institute of Clinical Biochemistry, University Hospital Hradec Kralove Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Pavla Paterova
- Department of Clinical Microbiology, University Hospital Hradec Kralove Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Eva Vejrazkova
- 4 th Department of Internal Medicine - Hematology, University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Jiri Cyrany
- 2 nd Department of Internal Medicine - Gastroenterology, University Hospital Hradec Kralove Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Filip Gabalec
- 4 th Department of Internal Medicine - Hematology, University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Miroslav Podhola
- The Fingerland´s Department of Patology, University Hospital Hradec Kralove Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Pavel Zak
- 4 th Department of Internal Medicine - Hematology, University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
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Abstract
PURPOSE OF REVIEW The review summarizes the epidemiology, risk factors, clinical presentation, diagnosis and management of the most important etiologic agents of infectious diarrhea in critically ill transplant recipients. RECENT FINDINGS Diarrhea, frequently caused by infectious pathogens, can cause significant morbidity and mortality in transplant recipients. Diarrhea can lead to severe dehydration, acute renal failure, medication toxicity, rejection, graft-versus-host disease and impairs patients' quality of life. Opportunistic infectious pathogens can pose significant diagnostic and therapeutic challenges in immunocompromised hosts. SUMMARY In transplant recipients, it is vital to differentiate infectious from noninfectious diarrhea to adequately manage their therapeutic approach. Supportive measures and reduction in immunosuppression are essential for the treatment management.
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Wong YJ, Tan BH, Leow WQ, Mesenas SJ. Cytomegalovirus infection masquerading as gastric carcinoma in an immune-compromised host. PROCEEDINGS OF SINGAPORE HEALTHCARE 2018; 27:63-66. [DOI: 10.1177/2010105817731797] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
A 63-year-old man post-renal transplantation on immunosuppressants presented with reflux symptoms for one month. Significant medical history included a history of upper gastrointestinal bleeding, insulin-dependent diabetes mellitus and ischemic heart disease. Barium meal showed a large plaque-like lesion along greater curvature suspicious of malignancy. Gastroscopy revealed a large polyploidal gastric mass which was biopsied. Histological result showed numerous cytomegalovirus (CMV) viral inclusions within hyperplastic gastric mucosa without dysplasia or neoplasm. The findings were consistent with CMV gastric polyp. Following treatment with antiviral therapy and reduction in immunosuppressants, the CMV gastric polyp became smaller. This highlights the importance of considering CMV as a differential of gastric mass in an immunosuppressed host as treatment options varied between surgery and antiviral therapy.
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Affiliation(s)
- Yu Jun Wong
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Ban Hock Tan
- Department of Infectious Disease, Singapore General Hospital, Singapore
| | - Wei Qiang Leow
- Department of Anatomical Pathology, Singapore General Hospital, Singapore
| | - Steven Joseph Mesenas
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
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Puttarajappa CM, Hariharan S, Smith KJ. A Markov Analysis of Screening for Late-Onset Cytomegalovirus Disease in Cytomegalovirus High-Risk Kidney Transplant Recipients. Clin J Am Soc Nephrol 2018; 13:290-298. [PMID: 29025787 PMCID: PMC5967425 DOI: 10.2215/cjn.05080517] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Accepted: 09/06/2017] [Indexed: 01/15/2023]
Abstract
BACKGROUND AND OBJECTIVES Management strategies are unclear for late-onset cytomegalovirus infection occurring beyond 6 months of antiviral prophylaxis in cytomegalovirus high-risk (cytomegalovirus IgG positive to cytomegalovirus IgG negative) kidney transplant recipients. Hybrid strategies (prophylaxis followed by screening) have been investigated but with inconclusive results. There are clinical and potential cost benefits of preventing cytomegalovirus-related hospitalizations and associated increased risks of patient and graft failure. We used decision analysis to evaluate the utility of postprophylaxis screening for late-onset cytomegalovirus infection. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We used the Markov decision analysis model incorporating costs and utilities for various cytomegalovirus clinical states (asymptomatic cytomegalovirus, mild cytomegalovirus infection, and cytomegalovirus infection necessitating hospitalization) to estimate cost-effectiveness of postprophylaxis cytomegalovirus screening strategies. Five strategies were compared: no screening and screening at 1-, 2-, 3-, or 4-week intervals. Progression to severe cytomegalovirus infection was modeled on cytomegalovirus replication kinetics. Incremental cost-effectiveness ratios were calculated as a ratio of cost difference between two strategies to difference in quality-adjusted life-years starting with the low-cost strategy. One-way and probabilistic sensitivity analyses were performed to test model's robustness. RESULTS There was an incremental gain in quality-adjusted life-years with increasing screening frequency. Incremental cost-effectiveness ratios were $783 per quality-adjusted life-year (every 4 weeks over no screening), $1861 per quality-adjusted life-year (every 3 weeks over every 4 weeks), $10,947 per quality-adjusted life-year (every 2 weeks over every 3 weeks), and $197,086 per quality-adjusted life-year (weekly over every 2 weeks). Findings were sensitive to screening cost, cost of hospitalization, postprophylaxis cytomegalovirus incidence, and graft loss after cytomegalovirus infection. No screening was favored when willingness to pay threshold was <$14,000 per quality-adjusted life-year, whereas screening weekly was favored when willingness to pay threshold was >$185,000 per quality-adjusted life-year. Screening every 2 weeks was the dominant strategy between willingness to pay range of $14,000-$185,000 per quality-adjusted life-year. CONCLUSIONS In cytomegalovirus high-risk kidney transplant recipients, compared with no screening, screening for postprophylactic cytomegalovirus viremia is associated with gains in quality-adjusted life-years and seems to be cost effective. A strategy of screening every 2 weeks was the most cost-effective strategy across a wide range of willingness to pay thresholds.
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Affiliation(s)
- Chethan M. Puttarajappa
- Thomas E. Starzl Transplantation Institute, Pittsburgh, Pennsylvania; and
- Renal-Electrolyte Division, Department of Medicine and
| | - Sundaram Hariharan
- Thomas E. Starzl Transplantation Institute, Pittsburgh, Pennsylvania; and
- Renal-Electrolyte Division, Department of Medicine and
| | - Kenneth J. Smith
- Department of Medicine, Section of Decision Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania
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An J, Brownell J, Barker D, Stockinger T, Brady R, Cebe K, Baur R. Cytomegalovirus Colitis Masquerading as Apple-Core Lesion after Systemic Chemotherapy in a Patient with Relapsed Acute Myeloid Leukemia. Case Rep Oncol Med 2018; 2018:5683417. [PMID: 29755802 PMCID: PMC5884229 DOI: 10.1155/2018/5683417] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Revised: 12/31/2017] [Accepted: 02/10/2018] [Indexed: 11/17/2022] Open
Abstract
We report the case of a 71-year-old male with relapsed acute myeloid leukemia who developed cytomegalovirus (CMV) colitis presenting as an apple-core lesion during induction chemotherapy. CMV infection occurs rarely during induction chemotherapy for acute myeloid leukemia. CMV infection is usually observed in patients with acquired immune deficiency syndrome (AIDS) and in those on immunosuppressive agents following bone marrow transplant. Although rare, CMV colitis should be considered in patients who are critically ill after systemic chemotherapy as it can cause significant morbidity and mortality.
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Affiliation(s)
- Jong An
- 1Department of Hematology and Oncology Service, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, TX 78234, USA
| | - Jason Brownell
- 2Department of Internal Medicine, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, TX 78234, USA
| | - Darrell Barker
- 3Department of Gastroenterology, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, TX 78234, USA
| | - Theresa Stockinger
- 4Department of Pathology, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, TX 78234, USA
| | - Robert Brady
- 4Department of Pathology, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, TX 78234, USA
| | - Katherine Cebe
- 4Department of Pathology, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, TX 78234, USA
| | - Russell Baur
- 1Department of Hematology and Oncology Service, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, TX 78234, USA
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Vincenzi R, Fonseca EA, Chapchap P, Machado MCC, Roda KMO, Candido HL, Benavides MR, D'Assuncao MA, Afonso RC, Turine P, Marson FP, Neto JS. Pancreas-preserving duodenectomy after living donor liver transplantation for invasive cytomegalovirus disease. Pediatr Transplant 2017; 21. [PMID: 28881059 DOI: 10.1111/petr.13059] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/09/2017] [Indexed: 12/15/2022]
Abstract
CMV infection plays an important role in the postoperative course following solid organ transplantation. We present the case of an 11-year-old male patient who underwent LDLT due to severe hepatopulmonary syndrome and biliary cirrhosis. Four weeks after LDLT, he developed persistent GI bleeding and was subjected to repeated endoscopic treatment and radiological arterial embolization to stop the bleeding from duodenal ulcers. Diagnostic workup was negative for CMV disease. Because the bleeding persisted, surgical treatment was indicated, and a pancreas-preserving duodenectomy was performed. Immunohistochemical staining of the surgical specimen demonstrated diffuse endothelial infiltration by CMV. Despite ganciclovir treatment, the patient developed new erosions in the jejunal mucosa and melena; ganciclovir was discontinued, and foscarnet was started, resulting in clinical improvement and the cessation of bleeding. This case highlights the technical aspects of performing a complex upper GI resection in a patient recently subjected to LDLT, taking care to avoid injury to the previous liver graft anastomosis and restore GI continuity. Moreover, CMV tissue-invasive disease compartmentalized in the GI tract may be difficult to diagnose, as indicated by the negative results of antigenemia and PCR assays and endoscopic superficial mucosal biopsies.
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Affiliation(s)
- Rodrigo Vincenzi
- Hepatology and Liver Transplantation, Hospital Sirio-Libanes, Sao Paulo, SP, Brazil.,A.C. Camargo Cancer Center, Sao Paulo, SP, Brazil
| | - Eduardo A Fonseca
- Hepatology and Liver Transplantation, Hospital Sirio-Libanes, Sao Paulo, SP, Brazil.,A.C. Camargo Cancer Center, Sao Paulo, SP, Brazil
| | - Paulo Chapchap
- Hepatology and Liver Transplantation, Hospital Sirio-Libanes, Sao Paulo, SP, Brazil
| | | | - Karina M O Roda
- Hepatology and Liver Transplantation, Hospital Sirio-Libanes, Sao Paulo, SP, Brazil.,A.C. Camargo Cancer Center, Sao Paulo, SP, Brazil
| | - Helry L Candido
- Hepatology and Liver Transplantation, Hospital Sirio-Libanes, Sao Paulo, SP, Brazil.,A.C. Camargo Cancer Center, Sao Paulo, SP, Brazil
| | - Marcel R Benavides
- Hepatology and Liver Transplantation, Hospital Sirio-Libanes, Sao Paulo, SP, Brazil.,A.C. Camargo Cancer Center, Sao Paulo, SP, Brazil
| | - Marco A D'Assuncao
- Gastrointestinal Endoscopy Unit, Hospital Sirio-Libanes, Sao Paulo, SP, Brazil
| | - Rogerio C Afonso
- Hepatology and Liver Transplantation, Hospital Sirio-Libanes, Sao Paulo, SP, Brazil.,A.C. Camargo Cancer Center, Sao Paulo, SP, Brazil
| | - Plinio Turine
- Hepatology and Liver Transplantation, Hospital Sirio-Libanes, Sao Paulo, SP, Brazil.,A.C. Camargo Cancer Center, Sao Paulo, SP, Brazil
| | - Fernando P Marson
- Gastrointestinal Endoscopy Unit, Hospital Sirio-Libanes, Sao Paulo, SP, Brazil
| | - João Seda Neto
- Hepatology and Liver Transplantation, Hospital Sirio-Libanes, Sao Paulo, SP, Brazil.,A.C. Camargo Cancer Center, Sao Paulo, SP, Brazil
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42
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43
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Yong MK, Cameron PU, Slavin M, Morrissey CO, Bergin K, Spencer A, Ritchie D, Cheng AC, Samri A, Carcelain G, Autran B, Lewin SR. Identifying Cytomegalovirus Complications Using the Quantiferon-CMV Assay After Allogeneic Hematopoietic Stem Cell Transplantation. J Infect Dis 2017; 215:1684-1694. [PMID: 28431019 DOI: 10.1093/infdis/jix192] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Background A simple test to identify recovery of CMV-specific T-cell immunity following hematopoietic stem cell transplantation (HSCT) could assist clinicians in managing CMV-related complications. Methods In an observational, multicenter, prospective study of 94 HSCT recipients we evaluated CMV-specific T-cell immunity at baseline, 3, 6, 9, and 12 months after transplant using the Quantiferon-CMV, an enzyme-linked immunosorbent spot assay (ELISpot), and intracellular cytokine staining. Results At 3 months after HSCT, participants who developed CMV disease (n = 8) compared with CMV reactivation (n = 26) or spontaneous viral control (n = 25) had significantly lower CD8+ T-cell production of interferon-γ (IFN-γ) in response to CMV antigens measured by Quantiferon-CMV (P = .0008). An indeterminate Quantiferon-CMV result had a positive predictive value of 83% and a negative predictive value of 98% for identifying participants at risk of further CMV reactivation. Participants experiencing CMV reactivation compared with patients without CMV reactivation had a reduced proportion of polyfunctional (IFN-γ+/tumor necrosis factor α-positive) CD4+ and CD8+ T cells and a higher proportion of interleukin 2-secreting cells (P = .01 and P = .002, respectively). Conclusions Quantifying CMV-specific T-cell immunity after HSCT can identify participants at increased risk of clinically relevant CMV-related outcomes.
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Affiliation(s)
- Michelle K Yong
- Department of Infectious Diseases, Monash University and Alfred Hospital.,Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital
| | - Paul U Cameron
- Department of Infectious Diseases, Monash University and Alfred Hospital.,Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital
| | - Monica Slavin
- Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital.,Victorian Infectious Diseases Service, Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity.,Peter MacCallum Cancer Centre
| | - C Orla Morrissey
- Department of Infectious Diseases, Monash University and Alfred Hospital.,Department of Haematology, Monash University and Alfred Hospital
| | - Krystal Bergin
- Department of Haematology, Monash University and Alfred Hospital
| | - Andrew Spencer
- Department of Haematology, Monash University and Alfred Hospital
| | - David Ritchie
- Department of Clinical Haematology and Bone Marrow Transplant Service, Royal Melbourne Hospital.,Department of Medicine, University of Melbourne, Melbourne, Australia
| | - Allen C Cheng
- Department of Infectious Diseases, Monash University and Alfred Hospital
| | - Assia Samri
- Institut National de la Sante et de la Recherche Medicale, U1135, Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universités, University Pierre et Marie Curie.,Assistance Publique-Hopitaux de Paris, Hôpital Pitié-Salpêtrière, Département d'Immunologie, France
| | - Guislaine Carcelain
- Institut National de la Sante et de la Recherche Medicale, U1135, Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universités, University Pierre et Marie Curie.,Assistance Publique-Hopitaux de Paris, Hôpital Pitié-Salpêtrière, Département d'Immunologie, France
| | - Brigitte Autran
- Institut National de la Sante et de la Recherche Medicale, U1135, Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universités, University Pierre et Marie Curie.,Assistance Publique-Hopitaux de Paris, Hôpital Pitié-Salpêtrière, Département d'Immunologie, France
| | - Sharon R Lewin
- Department of Infectious Diseases, Monash University and Alfred Hospital.,Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital
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Aizawa R, Matsumoto S, Uneno Y, Nishikawa Y, Ozaki Y, Mori Y, Kanai M, Ishida Y, Sakanaka K, Hiraoka M, Muto M. Severe esophagitis associated with cytomegalovirus during concurrent chemoradiotherapy for esophageal cancer. Jpn J Clin Oncol 2017; 47:885-888. [PMID: 28591845 DOI: 10.1093/jjco/hyx083] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Accepted: 05/24/2017] [Indexed: 12/31/2022] Open
Abstract
Although radiation esophagitis is one of the most common adverse events that occurs during chemoradiotherapy (CRT) in patients with esophageal cancer, CRT-associated cytomegalovirus (CMV) esophagitis is rare. CMV esophagitis typically occurs in patients with an immunosuppressed status. Here we report a case of CMV esophagitis during CRT initially treated as radiation esophagitis. A 64-year-old man with mid-thoracic esophageal cancer was admitted to our hospital with clinical stage cT4bN1M1 (supraclavicular lymph node metastasis) Stage IV according to the UICC ver. 7 guidelines, and he was administered definitive concurrent CRT. From the 39th day of CRT onwards, he presented with a sustained fever and severe odynophagia that was resistant to antibiotic therapy. An esophagoscopy revealed severe esophagitis with a circumferential ulcer throughout the entire esophagus, and CMV esophagitis was clinically suspected because of positive result of CMV antigenemia. Subsequently, antiviral therapy for CMV provided dramatic relief of his symptoms. Later, CMV DNA was confirmed with a polymerase chain reaction in the biopsy specimen.The symptoms of CMV esophagitis resemble those of radiation esophagitis and can make the diagnosis difficult. Thus, CMV esophagitis associated CRT may be overlooked or masked by radiation esophagitis and can cause a delay in healing. Therefore, CMV esophagitis may be considered when severe intractable esophagitis is observed during CRT.
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Affiliation(s)
- Rihito Aizawa
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shigemi Matsumoto
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | - Yu Uneno
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | | | - Yoshinao Ozaki
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | - Yukiko Mori
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | - Masashi Kanai
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | - Yuichi Ishida
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Katsuyuki Sakanaka
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | | | - Manabu Muto
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
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Trinh SA, Echenique IA, Penugonda S, Angarone MP. Optimal strategies for the diagnosis of community-onset diarrhea in solid organ transplant recipients: Less is more. Transpl Infect Dis 2017; 19. [PMID: 28170133 DOI: 10.1111/tid.12673] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Revised: 10/01/2016] [Accepted: 11/06/2016] [Indexed: 01/05/2023]
Abstract
BACKGROUND Diarrhea, a common complication after solid organ transplant (SOT), is associated with allograft failure and death. No evidence-based guidelines exist for the evaluation of diarrhea in SOT recipients. We performed a cost analysis to derive a testing algorithm for the diagnosis of community-onset diarrhea that minimizes costs without compromising diagnostic yields. DESIGN A cost analysis was performed on a retrospective cohort of 422 SOT admissions for community-onset diarrhea over an 18-month period. A stepwise testing model was applied on a population level to assess test costs relative to diagnostic yields. RESULTS Over an 18-month period, 1564 diagnostic tests were performed and 127 (8.1%) returned positive. Diagnostic testing accounted for $95 625 of hospital costs. The tests with the lowest cost per decrease in the false-omission rate (FOR) were stool Clostridium difficile polymerase chain reaction (PCR) ($156), serum cytomegalovirus quantitative PCR ($1529), stool norovirus (NV) PCR ($4673), and stool culture ($6804). A time-to-event analysis found no significant difference in the length of hospital stay between patients with and without NV testing (P=.520). CONCLUSIONS A stepwise testing strategy can reduce costs without compromising diagnostic yields. In the first-stage testing, we recommend assessment for C. difficile, cytomegalovirus, and food-borne bacterial pathogens. For persistent diarrheal episodes, second-stage evaluation should include stool NV PCR, Giardia/Cryptosporidium enzyme immunoassay, stool ova and parasite, reductions in immunosuppressive therapy, and possibly endoscopy. Although NV testing had a relatively low cost per FOR, we recommend NV testing during second-stage evaluation, as an NV diagnosis may not lead to changes in clinical management or further reductions in length of hospital stay.
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Affiliation(s)
- Sonya A Trinh
- Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Ignacio A Echenique
- Department of Infectious Diseases, Cleveland Clinic Florida, Weston, FL, USA
| | - Sudhir Penugonda
- Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Michael P Angarone
- Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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46
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Kim T, Lee YM, Lee SO, Choi SH, Kim YS, Woo JH, Sung H, Jung JH, Shin S, Kim YH, Kang YA, Lee YS, Lee JH, Lee JH, Lee KH, Park SK, Han DJ, Kim SH. Differences of cytomegalovirus diseases between kidney and hematopoietic stem cell transplant recipients during preemptive therapy. Korean J Intern Med 2016; 31:961-70. [PMID: 27055664 PMCID: PMC5016278 DOI: 10.3904/kjim.2015.079] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 05/22/2015] [Accepted: 06/30/2015] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND/AIMS Cytomegalovirus (CMV) surveillance and preemptive therapy is a widely-used strategy for preventing CMV disease in transplant recipients. However, there are limited data on the incidence and patterns of CMV disease during the preemptive period. Thus, we investigated the incidence and pattern of tissue-invasive CMV disease in CMV seropositive kidney transplantation (KT) and hematopoietic stem cell transplantation (HCT) recipients during preemptive therapy. METHODS We prospectively identified patients with tissue-invasive CMV disease among 664 KT (90%) and 496 HCT (96%) recipients who were D+/R+ (both donor and recipient seropositive) during a 4-year period. RESULTS The incidence rates of CMV disease were 4.1/100 person-years (4%, 27/664) in KT recipients and 5.0/100 person-years (4%, 21/496) in HCT recipients. Twenty-six (96%) of the KT recipients with CMV disease had gastrointestinal CMV, whereas 17 (81%) of the HCT recipients had gastrointestinal CMV and 4 (19%) had CMV retinitis. Thus, CMV retinitis was more common among HCT recipients (p = 0.03). All 27 KT recipients with CMV disease suffered abrupt onset of CMV disease before or during preemptive therapy; 10 (48%) of the 21 HCT recipients with CMV disease were also classified in this way but the other 11 (52%) were classified as CMV disease following successful ganciclovir preemptive therapy (p < 0.001). CONCLUSIONS The incidence of CMV disease was about 4% in both KT and HCT recipients during preemptive therapy. However, CMV retinitis and CMV disease as a relapsed infection were more frequently found among HCT recipients.
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Affiliation(s)
- Tark Kim
- Division of Infectious Diseases, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yu-Mi Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Infectious Diseases, Inje University Busan Paik Hospital, Busan, Korea
| | - Sang-Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang-Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jun Hee Woo
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Heungsup Sung
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Joo Hee Jung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Shin
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Hoon Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Ah Kang
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Shin Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jung-Hee Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Je-Hwan Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyoo-Hyung Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Su-Kil Park
- Department of Nephrology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Duck Jong Han
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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47
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Fisher C, Alexander J, Bhattacharya R, Rakita R, Kirby K, Boeckh M, Limaye A. Sensitivity of blood and tissue diagnostics for gastrointestinal cytomegalovirus disease in solid organ transplant recipients. Transpl Infect Dis 2016; 18:372-80. [DOI: 10.1111/tid.12531] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Revised: 12/17/2015] [Accepted: 01/21/2016] [Indexed: 12/12/2022]
Affiliation(s)
- C.E. Fisher
- Divisions of Allergy & Infectious Disease; Department of Medicine; University of Washington; Seattle Washington USA
- Vaccine and Infectious Disease Division; Fred Hutchinson Cancer Research Center; Seattle Washington USA
| | - J. Alexander
- Gastroenterology; Department of Medicine; University of Washington; Seattle Washington USA
| | - R. Bhattacharya
- Gastroenterology; Department of Medicine; University of Washington; Seattle Washington USA
| | - R.M. Rakita
- Divisions of Allergy & Infectious Disease; Department of Medicine; University of Washington; Seattle Washington USA
| | - K.A. Kirby
- Division of Geriatrics; San Francisco VA Medical Center and University of California; San Francisco California USA
| | - M. Boeckh
- Divisions of Allergy & Infectious Disease; Department of Medicine; University of Washington; Seattle Washington USA
- Vaccine and Infectious Disease Division; Fred Hutchinson Cancer Research Center; Seattle Washington USA
| | - A.P. Limaye
- Divisions of Allergy & Infectious Disease; Department of Medicine; University of Washington; Seattle Washington USA
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Abstract
ABSTRACT
Gastrointestinal infections in the immunocompromised host are caused by the common bacterial, viral, fungal, and parasitic agents that also cause infections in the immunocompetent host. Of special consideration is that immunocompromised patients may be at increased risk for infection or disease severity and by pathogens not seen in the competent host. This chapter reviews the various agents, risk factors, and diagnostic approaches to detect gastrointestinal infections in this patient population.
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Coussement J, Steensels D, Nollevaux MC, Bogaerts P, Dumonceaux M, Delaere B, Froidure A. When polymerase chain reaction does not help: cytomegalovirus pneumonitis associated with very low or undetectable viral load in both blood and bronchoalveolar lavage samples after lung transplantation. Transpl Infect Dis 2016; 18:284-7. [PMID: 26910136 PMCID: PMC7169703 DOI: 10.1111/tid.12515] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2015] [Revised: 12/21/2015] [Accepted: 12/30/2015] [Indexed: 12/19/2022]
Abstract
Cytomegalovirus (CMV) pneumonitis occurs frequently among solid organ transplant recipients and is classically associated with significant viral replication in both blood and bronchoalveolar lavage (BAL) samples. We present a case of a 64‐year‐old lung transplant recipient who presented with CMV pneumonitis that was diagnosed based on the association of viral inclusion in the BAL sample, rapid response to ganciclovir, and absence of other infectious etiology. Surprisingly, we observed very low or undetectable viral load both in blood and BAL samples. Diagnosis of CMV pneumonitis should rely on the association of clinical, pathological, radiological, and microbiological signs, while quantitative nucleic acid amplification testing should be interpreted with caution.
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Affiliation(s)
- J Coussement
- Department of Infectious Diseases, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
| | - D Steensels
- Department of Clinical Microbiology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - M-C Nollevaux
- Department of Pathology, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
| | - P Bogaerts
- Department of Microbiology, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
| | - M Dumonceaux
- Department of Pneumology and Lung Transplantation, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
| | - B Delaere
- Department of Infectious Diseases, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
| | - A Froidure
- Department of Pneumology and Lung Transplantation, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
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Gupta A, Loftus EV, De Felice KM, Khanna S. Letter: cytomegalovirus colitis in a patient treated with ipilimumab for metastatic melanoma - authors' reply. Aliment Pharmacol Ther 2016; 43:176. [PMID: 26638940 DOI: 10.1111/apt.13467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Affiliation(s)
- A Gupta
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - E V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - K M De Felice
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - S Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
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