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Scarpini S, Morigi F, Betti L, Dondi A, Biagi C, Lanari M. Development of a Vaccine against Human Cytomegalovirus: Advances, Barriers, and Implications for the Clinical Practice. Vaccines (Basel) 2021; 9:551. [PMID: 34070277 PMCID: PMC8225126 DOI: 10.3390/vaccines9060551] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/20/2021] [Accepted: 05/22/2021] [Indexed: 12/13/2022] Open
Abstract
Human cytomegalovirus (hCMV) is one of the most common causes of congenital infection in the post-rubella era, representing a major public health concern. Although most cases are asymptomatic in the neonatal period, congenital CMV (cCMV) disease can result in permanent impairment of cognitive development and represents the leading cause of non-genetic sensorineural hearing loss. Moreover, even if hCMV mostly causes asymptomatic or pauci-symptomatic infections in immunocompetent hosts, it may lead to severe and life-threatening disease in immunocompromised patients. Since immunity reduces the severity of disease, in the last years, the development of an effective and safe hCMV vaccine has been of great interest to pharmacologic researchers. Both hCMV live vaccines-e.g., live-attenuated, chimeric, viral-based-and non-living ones-subunit, RNA-based, virus-like particles, plasmid-based DNA-have been investigated. Encouraging data are emerging from clinical trials, but a hCMV vaccine has not been licensed yet. Major difficulties in the development of a satisfactory vaccine include hCMV's capacity to evade the immune response, unclear immune correlates for protection, low number of available animal models, and insufficient general awareness. Moreover, there is a need to determine which may be the best target populations for vaccine administration. The aim of the present paper is to examine the status of hCMV vaccines undergoing clinical trials and understand barriers limiting their development.
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Affiliation(s)
- Sara Scarpini
- Specialty School of Pediatrics, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (S.S.); (F.M.); (L.B.)
| | - Francesca Morigi
- Specialty School of Pediatrics, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (S.S.); (F.M.); (L.B.)
| | - Ludovica Betti
- Specialty School of Pediatrics, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (S.S.); (F.M.); (L.B.)
| | - Arianna Dondi
- Pediatric Emergency Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (C.B.); (M.L.)
| | - Carlotta Biagi
- Pediatric Emergency Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (C.B.); (M.L.)
| | - Marcello Lanari
- Pediatric Emergency Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (C.B.); (M.L.)
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2
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Lee JS, Kim S, Kim S, Ahn K, Min DH. Fluorometric Viral miRNA Nanosensor for Diagnosis of Productive (Lytic) Human Cytomegalovirus Infection in Living Cells. ACS Sens 2021; 6:815-822. [PMID: 33529521 DOI: 10.1021/acssensors.0c01843] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
A human cytomegalovirus (HCMV) causes a persistent asymptomatic infection in healthy individuals and possesses unexpected dangers to newborn babies, immunocompromised people, and organ transplant recipients because of stealth transmission. Thus, an early and accurate diagnosis of HCMV infection is crucial for prevention of unexpected transmission and progression of the severe diseases. The standard method of HCMV diagnosis depends on serology, antigen test, and polymerase chain reaction-based nucleic acid detection, which have advantages for each target molecule. However, the serological test for an antibody is an indirect method assuming the past virus infection, and antigen and viral nucleic acid testing demand laborious, complex multistep procedures for direct virus detection. Herein, we present an alternative simple and facile fluorometric biosensor composed of a graphene oxide nanocolloid and fluorescent peptide nucleic acid (PNA) probe to detect the HCMV infection by simply monitoring the virally encoded microRNA as a new biomarker of lytic virus infection. We verify the sensing of HCMV-derived microRNA accumulated within 72 h after HCMV infection and examine the diagnosis of HCMV in living cells. We proceed with the time course and concentration-dependent investigation of hcmv-miRNA sensing in living cells as a direct method of HCMV detection at the molecular level on the basis of an intracellular hcmv-miRNA expression profile and graphene oxide nanocolloid-based simple diagnostic platform. The fluorometric biosensor enables the sequence-specific binding to the target HCMV miRNAs in HCMV-infected fibroblasts and shows the quantitative detection capability of HCMV infection to be as low as 4.15 × 105 immunofluorescence focus unit (IFU)/mL of the virus titer at 48 h post-infection with picomolar sensitivity for HCMV miRNA.
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Affiliation(s)
- Ji-Seon Lee
- Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea
| | - Seongchan Kim
- Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea
| | - Sungchul Kim
- Center for RNA Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea
- School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea
| | - Kwangseog Ahn
- Center for RNA Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea
- School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea
| | - Dal-Hee Min
- Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea
- School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea
- Institute of Biotherapeutics Convergence Technology, Lemonex Inc., Seoul 08826, Republic of Korea
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3
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Zhou X, Jin N, Chen B. Human cytomegalovirus infection: A considerable issue following allogeneic hematopoietic stem cell transplantation. Oncol Lett 2021; 21:318. [PMID: 33692850 PMCID: PMC7933754 DOI: 10.3892/ol.2021.12579] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 12/23/2020] [Indexed: 12/11/2022] Open
Abstract
Cytomegalovirus (CMV) is an opportunistic virus, whereby recipients are most susceptible following allogeneic hematopoietic stem cell transplantation (allo-HSCT). With the development of novel immunosuppressive agents and antiviral drugs, accompanied with the widespread application of prophylaxis and preemptive treatment, significant developments have been made in transplant recipients with human (H)CMV infection. However, HCMV remains an important cause of short- and long-term morbidity and mortality in transplant recipients. The present review summarizes the molecular mechanism and risk factors of HCMV reactivation following allo-HSCT, the diagnosis of CMV infection following allo-HSCT, prophylaxis and treatment of HCMV infection, and future perspectives. All relevant literature were retrieved from PubMed and have been reviewed.
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Affiliation(s)
- Xinyi Zhou
- Department of Hematology and Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Nan Jin
- Department of Hematology and Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Baoan Chen
- Department of Hematology and Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China
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4
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Resistant or refractory cytomegalovirus infections after hematopoietic cell transplantation: diagnosis and management. Curr Opin Infect Dis 2020; 32:565-574. [PMID: 31567572 DOI: 10.1097/qco.0000000000000607] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE OF REVIEW Refractory or resistant cytomegalovirus (CMV) infections are challenging complications after hematopoietic cell transplantation (HCT). Most refractory or resistant CMV infections are associated with poor outcomes and increased mortality. Prompt recognition of resistant or refractory CMV infections, understanding the resistance pathways, and the treatment options in HCT recipients are imperative. RECENT FINDINGS New definitions for refractory and resistant CMV infections in HCT recipients have been introduced for future clinical trials. Interestingly, refractory CMV infections are more commonly encountered in HCT recipients when compared with resistant CMV infections. CMV terminase complex mutations in UL56, UL89, and UL51 could be associated with letermovir resistance; specific mutations in UL56 are the most commonly encountered in clinical practice. Finally, brincidofovir, maribavir, letermovir, and CMV-specific cytotoxic T-cell therapy expanded our treatment options for refractory or resistant CMV infections. SUMMARY Many advances have been made to optimize future clinical trials for management of refractory or resistant CMV infections, and to better understand new resistance mechanisms to novel drugs. New drugs or strategies with limited toxicities are needed to improve outcomes of difficult to treat CMV infections in HCT recipients.
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Engelmann C, Sterneck M, Weiss KH, Templin S, Zopf S, Denk G, Eurich D, Pratschke J, Weiss J, Braun F, Welker MW, Zimmermann T, Knipper P, Nierhoff D, Lorf T, Jäckel E, Hau HM, Tsui TY, Perrakis A, Schlitt HJ, Herzer K, Tacke F. Prevention and Management of CMV Infections after Liver Transplantation: Current Practice in German Transplant Centers. J Clin Med 2020; 9:2352. [PMID: 32717978 PMCID: PMC7465768 DOI: 10.3390/jcm9082352] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/15/2020] [Accepted: 07/20/2020] [Indexed: 12/22/2022] Open
Abstract
Human cytomegalovirus (CMV) remains a major cause of mortality and morbidity in human liver transplant recipients. Anti-CMV therapeutics can be used to prevent or treat CMV in liver transplant recipients, but their toxicity needs to be balanced against the benefits. The choice of prevention strategy (prophylaxis or preemptive treatment) depends on the donor/recipient sero-status but may vary between institutions. We conducted a series of consultations and roundtable discussions with German liver transplant center representatives. Based on 20 out of 22 centers, we herein summarize the current approaches to CMV prevention and treatment in the context of liver transplantation in Germany. In 90% of centers, transient prophylaxis with ganciclovir or valganciclovir was standard of care in high-risk (donor CMV positive, recipient CMV naive) settings, while preemptive therapy (based on CMV viremia detected during (bi) weekly PCR testing for circulating CMV-DNA) was preferred in moderate- and low-risk settings. Duration of prophylaxis or intense surveillance was 3-6 months. In the case of CMV infection, immunosuppression was adapted. In most centers, antiviral treatment was initiated based on PCR results (median threshold value of 1000 copies/mL) with or without symptoms. Therefore, German transplant centers report similar approaches to the prevention and management of CMV infection in liver transplantation.
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Affiliation(s)
- Cornelius Engelmann
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charité University Medicine Berlin, 13353 Berlin, Germany;
- Institute for Liver and Digestive Health, University College London, Royal Free Campus, London NW32PF, UK
- Section Hepatology, Clinic for Gastroenterology and Rheumatology, University Hospital Leipzig, 04103 Leipzig, Germany
| | - Martina Sterneck
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany;
| | - Karl Heinz Weiss
- Department of Gastroenterology and Hepatology, University of Heidelberg, 69117 Heidelberg, Germany;
| | - Silke Templin
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, 72076 Tübingen, Germany;
| | - Steffen Zopf
- Department of Medicine 1, University of Erlangen-Nürnberg, 91054 Erlangen, Germany;
| | - Gerald Denk
- Medical clinic and policlinic II, Campus Grosshadern, Ludwig Maximilians University (LMU), 80333 Munich, Germany;
- Transplantation Center Munich, University Hospital, 81377 LMU Munich, Germany
| | - Dennis Eurich
- Department of Surgery Campus Charité Mitte/Campus Virchow-Klinikum, 13353 Berlin, Germany; (D.E.); (J.P.)
| | - Johann Pratschke
- Department of Surgery Campus Charité Mitte/Campus Virchow-Klinikum, 13353 Berlin, Germany; (D.E.); (J.P.)
| | - Johannes Weiss
- Department of Medicine II, University Hospital Würzburg, 97080 Würzburg, Germany;
| | - Felix Braun
- Department of General, Visceral, Thoracic, Transplant and Pediatric Surgery, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany;
| | - Martin-Walter Welker
- Department of Medicine I, University Hospital Frankfurt, 60590 Frankfurt, Germany;
| | - Tim Zimmermann
- Department of Medicine, Hepatology, University of Mainz, 55101 Mainz, Germany;
| | - Petra Knipper
- Department of Internal Medicine I, University Hospital Bonn, 53127 Bonn, Germany;
| | - Dirk Nierhoff
- Department of Gastroenterology and Hepatology, University Hospital Köln, 50937 Köln, Germany;
| | - Thomas Lorf
- Clinic for General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany;
| | - Elmar Jäckel
- Department of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, 30625 Hannover, Germany;
| | - Hans-Michael Hau
- Department of Visceral, Transplantation, Thoracic, and Vascular Surgery, University Hospital Leipzig, 04103 Leipzig, Germany;
| | - Tung Yu Tsui
- Section of Oncological Surgery and Transplantation, Rostock University Medical Center, 18057 Rostock, Germany;
| | - Aristoteles Perrakis
- Department of General, Visceral, Vascular and Transplant Surgery, University Hospital Magdeburg, 39120 Magdeburg, Germany;
| | | | - Kerstin Herzer
- Knappschafts-Hospital Bad Neuenahr, Deutsche Rentenversicherung, Knappschaft-Bahn-See, 53474 Bad Neuenahr-Ahrweiler, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charité University Medicine Berlin, 13353 Berlin, Germany;
- Department of Medicine III, University Hospital Aachen, 52074 Aachen, Germany
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6
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Cytomegalovirus encephalitis in immunocompetent infants: A 15-year retrospective study at a single center. Int J Infect Dis 2019; 82:106-110. [DOI: 10.1016/j.ijid.2019.02.045] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Revised: 12/27/2018] [Accepted: 02/26/2019] [Indexed: 11/23/2022] Open
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Association between CMV and Invasive Fungal Infections After Autologous Stem Cell Transplant in Lymphoproliferative Malignancies: Opportunistic Partnership or Cause-Effect Relationship? Int J Mol Sci 2019; 20:ijms20061373. [PMID: 30893777 PMCID: PMC6471891 DOI: 10.3390/ijms20061373] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 03/11/2019] [Accepted: 03/14/2019] [Indexed: 12/12/2022] Open
Abstract
Unlike allogeneic transplant, autologous stem cell transplantation (ASCT) represents a procedure with a low-risk of cytomegalovirus (CMV) symptomatic reactivation-infection/end-organ disease (CMV complications) and invasive fungal disease (IFD). However, novel drugs for the treatment of lymphoproliferative malignancies could cause an increase of such opportunistic infections, even after ASCT. To the best of our knowledge, there are no published data demonstrating an association between CMV and IFD in the autologous setting, while this association has been widely reported in allogeneic transplantation. We have reviewed our series of 347 ASCT in myeloma and lymphoma patients performed over a period of 14 years with the aim of investigating the descriptive and analytical epidemiology of bacterial, CMV and IFD complications, focusing on the association between CMV and IFD. Patients with myeloma have significantly fewer bacterial infections and IFD than patients with lymphoma, but a similar rate of CMV complications. Descriptive epidemiological data are consistent with the literature, indicating an overall incidence of 36%, 3.5% and 15.5% for bacterial infections, IFD and CMV complications, with a case mortality rate of 4%, 16.7% and 3.7%, respectively. A strong correlation between CMV and IFD exists, with 8 cases of IFD out of a total of 12 presenting a CMV complication. At multivariate analysis, a diagnosis of lymphoma, ≥3 previous treatment lines and age ≥60 years were found to be independent risk factors for IFD. Duration of neutropenia (ANC < 500/mm3) ≥7 days represents an independent risk factor for CMV complications, where neutropenia most likely represents a crude surrogate biomarker indicating a deeper and longer state of overall immunosuppression. From our data we conclude that (1) myeloma patients are at lower risk of bacterial infections and IFD as compared with lymphoma patients but are at equal risk of CMV complications, most likely as a consequence of a selective impact of bortezomib on Herpes Viruses infection control; (2) a significant association exists between CMV and IFD, although a possible cause-effect relationship remains to be determined; (3) IFD is a rare complication after ASCT but burdened by a mortality rate of about 17%, with peak rates in older lymphoma patients who underwent more intensive therapeutic regimens.
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Jaing TH, Chang TY, Chen SH, Wen YC, Yu TJ, Lee CF, Yang CP, Tsay PK. Factors associated with cytomegalovirus infection in children undergoing allogeneic hematopoietic stem-cell transplantation. Medicine (Baltimore) 2019; 98:e14172. [PMID: 30681583 PMCID: PMC6358375 DOI: 10.1097/md.0000000000014172] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
While preemptive therapy with ganciclovir (GCV) for cytomegalovirus (CMV) infection is used following allogeneic hematopoietic stem-cell transplantation (HSCT), risk factors for CMV infection in children undergoing HSCT are poorly understood.We studied CMV reactivation following allogeneic HSCT by retrospectively analyzing pediatric patients who received allogeneic HSCT and preemptive GCV therapy between 1998 and 2016. The level of viremia requiring preemptive GCV therapy was >1 CMV antigen-positive cells per 5 × 10 leukocytes during the antigenemia assay era and >1000 copies/mL in the polymerase chain reaction era. Among 290 at-risk patients, 54 (18.6%) patients had primary CMV infection or CMV reactivation occurring at a median of 76 days (range, 7-234) following HSCT. CMV reactivation occurred in 28.2% (44/156) of CMV-seropositive transplant recipients at a median of 26 days posttransplant.Univariate and multivariate analyses revealed statistically significant relationships between CMV infection and grade III-IV acute graft-vs-host disease, seronegative donor/seropositive recipient combination, and unrelated/mismatched donors. The remaining demographic factors were not predictive of CMV infection.The seronegative donor/seropositive recipient combination for HSCT was associated with an incomplete response to antiviral therapy. Human leukocyte antigen identical donors were the best choice for patients undergoing allogeneic HSCT to reduce the incidence of CMV disease and mortality.
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Affiliation(s)
- Tang-Her Jaing
- Division of Hematology/Oncology, Department of Pediatrics, Chang Gung Children's Hospital
| | - Tsung-Yen Chang
- Division of Hematology/Oncology, Department of Pediatrics, Chang Gung Children's Hospital
| | - Shih-Hsiang Chen
- Division of Hematology/Oncology, Department of Pediatrics, Chang Gung Children's Hospital
| | | | | | - Ching-Fen Lee
- Division of Clinical Pharmacy, Department of Pharmacy, Chang Gung Memorial Hospital
| | - Chao-Ping Yang
- Division of Hematology/Oncology, Department of Pediatrics, Chang Gung Children's Hospital
| | - Pei-Kwei Tsay
- Department of Public Health and Center of Biostatistics, College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Hildenbrand C, Wedekind L, Li G, vonRentzell JE, Shah K, Rooney P, Harrington AT, Zhao RY. Clinical evaluation of Roche COBAS ® AmpliPrep/COBAS ® TaqMan ® CMV test using nonplasma samples. J Med Virol 2018; 90:1611-1619. [PMID: 29797374 DOI: 10.1002/jmv.25226] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Accepted: 05/10/2018] [Indexed: 11/11/2022]
Abstract
Cytomegalovirus (CMV) infection is a leading cause of loss of hearing, vision, and mental retardation in congenitally infected children. It is also associated with complications of organ transplant and opportunistic HIV coinfection. The Roche COBAS® AmpliPrep/COBAS® TaqMan® CMV test is an FDA-approved test that measures CMV DNA viral load in plasma for the diagnosis and management of patients at risk of CMV-associated diseases. Besides plasma, CMV is often found in bronchoalveolar lavage (BAL), cerebrospinal fluid (CSF), and urine. Thus, monitoring of CMV for critical care of patients in these nonplasma samples becomes necessary. The objective of this study was to conduct an analytic and clinical feasibility study of the Roche CMV test in BAL, CSF, and urine. The lower limit of detection, analytic measurement range, assay sensitivity, specificity, and precision were determined. Results of this study showed that the lower limit of detections were 50, 100, and 300 IU/mL for BAL, CSF, or urine, respectively. The analytic measurement ranges were from log10 2.48 to log10 5.48. The assay specificity was 94.4% for BAL and 100% for CSF and urine. The assay precision was all within the acceptable range. The performance of Roche test was further compared with 2 comparators including the RealTime CMV assay (Abbott Molecular) and a CMV Quantitative Polymerase Chain Reaction test (Vela Diagnostics). There was a general positive correlation between the Roche method and the Abbott or the Vela method. Overall, this study suggests that the Roche CMV test is suitable for the quantification of CMV viral load DNA in the described nonplasma samples.
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Affiliation(s)
- Cynthia Hildenbrand
- Molecular Diagnostics Laboratory, Universtiy of Maryland Medical Center, Baltimore, Maryland
| | - Laura Wedekind
- Molecular Diagnostics Laboratory, Universtiy of Maryland Medical Center, Baltimore, Maryland
| | - Ge Li
- Division of Molecular Pathology, Department of Pathololgy, University of Maryland School of Medicine, Baltimore, Maryland
| | | | | | | | - Amanda T Harrington
- Department of Pathology, Loyola University Medical Center, Chicago, Illinois
| | - Richard Y Zhao
- Molecular Diagnostics Laboratory, Universtiy of Maryland Medical Center, Baltimore, Maryland.,Division of Molecular Pathology, Department of Pathololgy, University of Maryland School of Medicine, Baltimore, Maryland
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Tang ER, Chapman T, Finn LS, Leger KJ. Perforated jejunitis in a child with acute lymphoblastic leukemia treated with pegaspargase. Radiol Case Rep 2018; 13:568-572. [PMID: 29988797 PMCID: PMC6030564 DOI: 10.1016/j.radcr.2018.02.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Accepted: 02/07/2018] [Indexed: 01/19/2023] Open
Abstract
Survival rates of children with acute lymphoblastic leukemia have improved since the incorporation of asparaginase in the treatment protocol, but the medication has potential serious complications, including vascular thrombosis. Here, we describe the case of a 13-year-old boy with pre-T-cell acute lymphoblastic leukemia whose treatment course was complicated by perforated jejunitis requiring resection of a portion of his small bowel. Pathologic assessment showed transmural ischemia, mesenteric venous and arterial thrombi, and scattered cytomegalovirus inclusion bodies. Pediatric mesenteric ischemia is rare, and its consideration in patients treated with asparaginase is discussed.
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Affiliation(s)
- Elizabeth R Tang
- Department of Radiology, Seattle Children's Hospital, University of Washington School of Medicine, 4800 Sand Point Way NE, Seattle, WA 98105, USA
| | - Teresa Chapman
- Department of Radiology, Seattle Children's Hospital, University of Washington School of Medicine, 4800 Sand Point Way NE, Seattle, WA 98105, USA
| | - Laura S Finn
- Department of Pathology, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA
| | - Kasey J Leger
- Department of Pediatrics, Division of Hematology-Oncology, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA
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11
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Al-Eyadhy AA, Hasan G, Bassrawi R, Al-Jelaify M, Temsah MH, Alhaboob A, Al-Sohime F, Alabdulhafid M. Cytomegalovirus associated severe pneumonia, multi-organ failure and Ganciclovir associated arrhythmia in immunocompetent child. J Infect Chemother 2017; 23:844-847. [PMID: 28888855 DOI: 10.1016/j.jiac.2017.08.003] [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: 03/25/2017] [Revised: 07/28/2017] [Accepted: 08/09/2017] [Indexed: 11/24/2022]
Abstract
Cytomegalovirus (CMV) can rarely cause severe manifestations in immunocompetent individuals. Hereby, we report a twelve-year-old boy who presented with tachycardia, tachypnea, fever and leukocytosis, which progressed to hypoxemic respiratory failure and severe acute respiratory distress syndrome (ARDS). Subsequently, he developed multi-organ failure despite the ongoing full supportive care and empiric broad spectrum antibiotics. Cytomegalovirus infection was diagnosed by Polymerase Chain Reaction (PCR) in blood and histopathological examination of lung biopsy. Immunological work up for the child was unremarkable. Ganciclovir therapy was introduced and showed significant improvement until full recovery. However, our patient developed transient heart block as a rare complication for Ganciclovir therapy throughout his course. We present this case with literature review for the CMV infection associated morbidity and mortality among immunocompetent children.
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Affiliation(s)
- Ayman A Al-Eyadhy
- Pediatric Intensive Care Unit, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Gamal Hasan
- Pediatric Intensive Care Unit, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Assiut University Children Hospital, Assiut Faculty of Medicine, Assiut University, Assiut, Egypt.
| | - Rolan Bassrawi
- Department of Pediatrics, King Khalid University Hospital, King Saud University Medical City, Riyadh, Saudi Arabia
| | - Muneera Al-Jelaify
- Pharmacy Services, King Khalid University Hospital, King Saud University Medical City, Riyadh, Saudi Arabia
| | - Mohamad-Hani Temsah
- Pediatric Intensive Care Unit, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Prince Abdullah Bin Khaled Coeliac Disease Research Chair (PAK CDRC), Saudi Arabia
| | - Ali Alhaboob
- Pediatric Intensive Care Unit, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Fahad Al-Sohime
- Pediatric Intensive Care Unit, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Majed Alabdulhafid
- Pediatric Intensive Care Unit, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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12
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Yu Q, Jia P, Su L, Zhao H, Que C. Outcomes and prognostic factors of non-HIV patients with pneumocystis jirovecii pneumonia and pulmonary CMV co-infection: A Retrospective Cohort Study. BMC Infect Dis 2017; 17:392. [PMID: 28583135 PMCID: PMC5460484 DOI: 10.1186/s12879-017-2492-8] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2016] [Accepted: 05/24/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Pneumocystis jirovecii pneumonia (PJP) and pulmonary cytomegalovirus (CMV) infection are common opportunistic infections among immunocompromised patients. However, few studies have evaluated their co-infection, especially among non-HIV patients. Therefore, we aimed to evaluate the outcomes and prognostic factors among non-HIV patients with PJP according to their CMV infection status. METHODS This retrospective study evaluated non-HIV patients who were diagnosed with PJP between January 2009 and January2016.The patients were classified and compared according to their pulmonary CMV infection status (positive infection: bronchoalveolar lavage fluid [BALF] CMV DNA loads of >500copies/mL). RESULTS Among 70 non-HIV patients with PJP, we identified 38 patients (54.3%) with pulmonary CMV infection. There was no significant difference in the mortality rates for the two groups (p = 0.15). Pulmonary CMV infection was significantly more common among patients who were receiving glucocorticoids and immunosuppressants, compared to corticosteroids only (p = 0.02). Pulmonary CMV infection was also significantly associated with severe dyspnea, a lower PaO2/FiO2, and the presence of centrilobular nodules (p = 0.008). Higher CMV DNA loads in the BALF were positively associated with mortality (p = 0.012). CONCLUSIONS Combined therapy using corticosteroids and other immunosuppressants may be a risk factor for pulmonary CMV co-infection among patients with PJP. In addition, CMV pneumonia should be considered when centrilobular nodules and/or severe hypoxemia are observed in non-HIV patients with PJP. Furthermore, antiviral treatment should be promptly initiated for patients with a high CMV DNA load in BALF, based on their poor prognosis.
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Affiliation(s)
- Qing Yu
- Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, 100034, China
| | - Peng Jia
- Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, 100034, China
| | - Li Su
- Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, 100034, China
| | - Hong Zhao
- Department of Infectious Disease, Peking University First Hospital, Beijing, 100034, China
| | - Chengli Que
- Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, 100034, China.
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Mehravaran H, Makvandi M, Samarbaf Zade A, Neisi N, Kiani H, Radmehr H, Shahani T, Hoseini SZ, Ranjbari N, Nahid Samiei R. Association of Human Cytomegalovirus with Hodgkin’s Disease and Non-Hodgkin’s lymphomas. Asian Pac J Cancer Prev 2017; 18:593-597. [PMID: 28440608 PMCID: PMC5464470 DOI: 10.22034/apjcp.2017.18.3.593] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Background and Objective: The human cytomegalovirus (HCMV) can persist lifelong as a latent infection and may result in a series of disorders. Associations with both Hodgkin’s disease and non-Hodgkin´s lymphomas have been reported. Expression of the unique long (UL)138 gene of HCMV is linked with the viral latency phase while that of the immediate-early (IE)1 gene is typical of the viral replication phase in patients. This study conducted to determine the prevalence of CMV latent infection in histological tissue samples from patients with Hodgkin’s and Non-Hodgkin´s lymphomas. Material and Methods: A cross sectional study was carried out with a total of 50 paraffin embedded tissues blocks, including 25 samples for Hodgkin’s disease and 25 samples for non-Hodgkin´s lymphomas. After RNA extraction and cDNA preparation, detection of IE1 mRNA was conducted by RT-PCR and identification of mRNA UL138 was achieved by nested PCR. Results: Among 25 cases of Non-Hodgkin´s lymphoma, 5 (20%) were positive for UL 138 and 1 (4%) for both IE1 and UL 138. Among 25 cases of Hodgkin only 1 (4%) was positive for UL 138 and all were negative for IE1 .Conclusion: A relatively high 20% rate of expression of UL 138 was detected in patients with non-Hodgkin´s lymphoma, so that latent CMV infection may play a role in development of the disease.
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Affiliation(s)
- Hamide Mehravaran
- Health Research Institute, Infectious and Tropical Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Alam MM, Bayoumy M, Ali A, Alali M, Al-enezi B, Abosoudah I. Cytomegalovirus infection in children after bone marrow transplantation: Risk factors, clinical aspects and outcomes. ACTA ACUST UNITED AC 2016. [DOI: 10.1016/j.pid.2016.03.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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15
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Marchesi F, Pimpinelli F, Gumenyuk S, Renzi D, Palombi F, Pisani F, Romano A, Spadea A, Papa E, Canfora M, Ensoli F, Mengarelli A. Cytomegalovirus reactivation after autologous stem cell transplantation in myeloma and lymphoma patients: A single-center study. World J Transplant 2015; 5:129-136. [PMID: 26421265 PMCID: PMC4580927 DOI: 10.5500/wjt.v5.i3.129] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Revised: 06/12/2015] [Accepted: 07/08/2015] [Indexed: 02/05/2023] Open
Abstract
AIM: To determine the incidence of and the risk factors for cytomegalovirus (CMV) symptomatic infection and end-organ disease after autologous stem cell transplantation (ASCT).
METHODS: A total of 327 consecutive non CD34+ selected autografts performed from the Hematology and Stem Cell Transplantation Unit of Regina Elena National Cancer Institute of Rome (Italy) in the period comprised between January 2003 to January 2015, were reviewed. Over the 327 autografts, 201 were performed in patients with multiple myeloma, whereas the remaining 126 in patients affected by non-Hodgkin’s lymphoma and Hodgkin’s lymphoma. The patients who underwent an ASCT for an acute leukemia (n = 20) in the same period were excluded from this analysis. CMV DNA load in the blood has been determined by polymerase-chain reaction in the case of a clinical suspicion of reactivation, therefore, no routine monitoring strategy was adopted. In the presence of signs and symptoms of CMV reactivation an antiviral treatment was performed.
RESULTS: Overall, 36 patients (11%) required a specific antiviral treatment for a symptomatic CMV reactivation (n = 32) or an end-organ disease (n = 4). We observed 20 and 16 cases of CMV reactivation among lymphoma (16%) and myeloma patients (8%), respectively. Among cases of end-organ disease, 3 were diagnosed as interstitial pneumonia and one remaining case as hemorrhagic enteritis. All cases of CMV reactivation were observed in IgG seropositive patients, with no documented cases of primary CMV infection. All patients were treated with a specific antiviral therapy, with a global rate of hospitalization of 55%; four patients received intravenous immunoglobulins. Transplant-related mortality was significantly higher in patients who experienced a CMV reactivation (8.4% ± 4.7% vs 1.7% ± 0.8%; P = 0.047). In univariate analysis, a pre-transplant HBcIgG seropositivity, a diagnosis of T-cell non-Hodgkin’s lymphoma and higher median age at transplant were significantly associated with the risk of developing a clinically relevant CMV infection requiring specific antiviral therapy (P < 0.001, P = 0.042 and P = 0.004, respectively). In multivariate analysis, only a pre-transplant HBcIgG seropositivity (OR = 8.928, 95%CI: 1.991-33.321; P = 0.023) and a diagnosis of T-cell non-Hodgkin’s lymphoma (OR = 4.739, 95%CI: 1.511-11.112; P = 0.042) proved to be independent predictors of a post-transplant clinically relevant CMV reactivation.
CONCLUSION: A symptomatic CMV infection can occur in about 11% of adult patients with lymphoma or myeloma undergoing ASCT. A pre-transplant HBcIgG seropositivity and a diagnosis of T-cell non-Hodgkin’s lymphoma should be considered as independent predictor factors of CMV reactivation.
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Chen XF, Li TR, Yang H, Shao Y, Zhang J, Zhang W, Yu B, Wei Z, Wu B, Yu L. Detection of Two Drug-Resistance Mutants of the Cytomegalovirus by High-Resolution Melting Analysis. J Clin Lab Anal 2015; 30:319-25. [PMID: 25968338 DOI: 10.1002/jcla.21858] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Accepted: 04/07/2015] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Human cytomegalovirus (CMV) is an opportunistic pathogen that can be treated with ganciclovir. Mutations in the UL97 gene of CMV render the virus ganciclovir resistance. These include H520Q and C603W mutations, against which we developed a novel genotyping assay for their identification. METHODS PCR reactions were performed to amplify fragments of the UL97 gene containing H520Q or C603W mutations. High resolution melting analysis (HRMA) coupled with unlabeled DNA probes was employed to identify the shift in melting temperature of the probe-template complex, which reflexes the presence of point mutations. RESULTS Melting point analysis performed on the dimeric DNA of PCR products of UL97 gene could not identify mutations in the gene. When coupled to unlabeled probes, point mutations in UL97 can be identified by analyzing the melting curve of probe-template complex. When WT and mutant UL97 DNAs were mixed together to mimic heterogeneous viral population in clinical samples, the genotyping assay is sensitive enough to detect H520Q and C603W mutants that constitute 10% of total DNA input. CONCLUSION Probe-based HRMA is effective in detecting H520Q and C603W mutations in the UL97 gene of CMV.
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Affiliation(s)
- Xiao-Fan Chen
- Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China.,Department of Dermatology, Shenzhen Hospital Peking University, Shenzhen, Guangdong, China.,Shenzhen Key Lab for Translational Medicine of Dermatology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China
| | - Tian-Run Li
- Department of Intervention and Vascular Surgery, Peking University Third Hospital, Beijing, China
| | - Hong Yang
- Department of Clinical Laboratory, Shenzhen Hospital Peking University, Shenzhen, Guangdong, China
| | - Yong Shao
- Department of Dermatology, Shenzhen Hospital Peking University, Shenzhen, Guangdong, China.,Shenzhen Key Lab for Translational Medicine of Dermatology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China
| | - Jie Zhang
- Department of Dermatology, Shenzhen Hospital Peking University, Shenzhen, Guangdong, China.,Shenzhen Key Lab for Translational Medicine of Dermatology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China
| | - Wei Zhang
- Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China.,Shenzhen Key Lab for Translational Medicine of Dermatology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China
| | - Bo Yu
- Department of Dermatology, Shenzhen Hospital Peking University, Shenzhen, Guangdong, China.,Shenzhen Key Lab for Translational Medicine of Dermatology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China
| | - Zhun Wei
- Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China.,Shenzhen Key Lab for Translational Medicine of Dermatology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China
| | - Bo Wu
- Department of Dermatology, Shenzhen Hospital Peking University, Shenzhen, Guangdong, China.,Shenzhen Key Lab for Translational Medicine of Dermatology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China
| | - Lin Yu
- Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
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Prophylaxis for Infections Following Allogeneic Hematopoietic Stem Cell Transplantation. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2015. [DOI: 10.1097/ipc.0000000000000190] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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18
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Marchesi F, Pimpinelli F, Dessanti ML, Gumenyuk S, Palombi F, Pisani F, Romano A, Spadea A, Maschio M, Ensoli F, Mengarelli A. Evaluation of risk of symptomatic cytomegalovirus reactivation in myeloma patients treated with tandem autologous stem cell transplantation and novel agents: a single-institution study. Transpl Infect Dis 2014; 16:1032-8. [PMID: 25369809 DOI: 10.1111/tid.12309] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Revised: 08/18/2014] [Accepted: 08/23/2014] [Indexed: 01/12/2023]
Abstract
The introduction of proteasome inhibitors and/or immunomodulators in the treatment of myeloma has led to an increase in viral infections, particularly in the Herpesviridae family. Previous studies about the risk of cytomegalovirus (CMV) reactivation after autologous stem cell transplantation (ASCT) have examined the clinical outcome after the first ASCT; however, only 1 study to date has investigated the risk of CMV reactivation after a second transplantation. To address this issue, we performed a retrospective chart review on 78 consecutive myeloma patients (median age 56 years) who underwent a tandem non-CD34(+) selected ASCT after induction treatment with either conventional chemotherapy (n = 42) or with novel agents (n = 36), respectively. All subjects had been mobilized and conditioned with cyclophosphamide plus granulocyte colony-stimulating factor and melphalan alone, respectively. CMV DNA load in the blood has been determined by polymerase chain reaction in the case of a clinical suspicion of CMV reactivation; therefore, routine monitoring was not performed. Considering the outcome of both the first and the second transplantations, we observed a total of 13 episodes of symptomatic CMV reactivation (13/156, 8%), in 12 subjects (12/78, 15%), all successfully treated. Eight subjects experienced a CMV reactivation after the first ASCT (8/78, 10%); however, only 1 of them (1/8, 12%) experienced a CMV reactivation after the second transplantation. Conversely, 4 CMV reactivations (6%) were observed after the second transplantation in the group of 70 patients who did not experience a CMV reactivation after the first ASCT. No statistically significant difference was observed between first and second ASCT (8/78, 10% vs. 5/78, 6%; P = 0.767). Univariate analysis showed that a pre-transplant treatment with novel agents was the only baseline factor significantly associated with the occurrence of post-ASCT CMV symptomatic reactivation after the first transplant (odds ratio [OR]: 9.897; 95% confidence interval [CI]: 1.154-84.840; P = 0.021) but not after the second transplant (OR: 5.125; 95% CI: 0.546-48.119; P = 0.115). No end-organ disease or primary infection was documented. Our data suggest that second transplantation does not increase the risk of CMV reactivation in our patient population, when compared with the first one, and confirm the role of a pre-transplant treatment with novel agents as a risk factor for CMV symptomatic reactivation.
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Affiliation(s)
- F Marchesi
- Hematology and Stem Cell Transplantation Unit, Regina Elena National Cancer Institute, Rome, Italy
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Espigado I, de la Cruz-Vicente F, BenMarzouk-Hidalgo OJ, Gracia-Ahufinger I, Garcia-Lozano JR, Aguilar-Guisado M, Cisneros JM, Urbano-Ispizua A, Perez-Romero P. Timing of CMV-specific effector memory T cells predicts viral replication and survival after allogeneic hematopoietic stem cell transplantation. Transpl Int 2014; 27:1253-62. [DOI: 10.1111/tri.12406] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Revised: 05/26/2014] [Accepted: 07/20/2014] [Indexed: 12/29/2022]
Affiliation(s)
- Ildefonso Espigado
- Instituto de Biomedicina de Sevilla (IBIS); Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla; Sevilla Spain
- Clinical Hematology; Department of Hematology; Hospital Universitario Virgen del Rocio; Sevilla Spain
| | - Fátima de la Cruz-Vicente
- Instituto de Biomedicina de Sevilla (IBIS); Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla; Sevilla Spain
- Clinical Hematology; Department of Hematology; Hospital Universitario Virgen del Rocio; Sevilla Spain
| | - Omar J. BenMarzouk-Hidalgo
- Instituto de Biomedicina de Sevilla (IBIS); Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla; Sevilla Spain
- Unit of Infectious Disease, Microbiology, and Preventive Medicine; Hospital Universitario Virgen del Rocio; Sevilla Spain
| | - Irene Gracia-Ahufinger
- Instituto de Biomedicina de Sevilla (IBIS); Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla; Sevilla Spain
- Unit of Infectious Disease, Microbiology, and Preventive Medicine; Hospital Universitario Virgen del Rocio; Sevilla Spain
| | - Jose R. Garcia-Lozano
- Instituto de Biomedicina de Sevilla (IBIS); Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla; Sevilla Spain
- Immunology Service; Hospital Universitario Virgen del Rocio; Sevilla Spain
| | - Manuela Aguilar-Guisado
- Instituto de Biomedicina de Sevilla (IBIS); Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla; Sevilla Spain
- Unit of Infectious Disease, Microbiology, and Preventive Medicine; Hospital Universitario Virgen del Rocio; Sevilla Spain
| | - Jose M. Cisneros
- Instituto de Biomedicina de Sevilla (IBIS); Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla; Sevilla Spain
- Unit of Infectious Disease, Microbiology, and Preventive Medicine; Hospital Universitario Virgen del Rocio; Sevilla Spain
| | - Alvaro Urbano-Ispizua
- Instituto de Biomedicina de Sevilla (IBIS); Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla; Sevilla Spain
- Clinical Hematology; Department of Hematology; Hospital Universitario Virgen del Rocio; Sevilla Spain
| | - Pilar Perez-Romero
- Instituto de Biomedicina de Sevilla (IBIS); Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla; Sevilla Spain
- Unit of Infectious Disease, Microbiology, and Preventive Medicine; Hospital Universitario Virgen del Rocio; Sevilla Spain
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Maio GD, Rengucci C, Zoli W, Calistri D. Circulating and stool nucleic acid analysis for colorectal cancer diagnosis. World J Gastroenterol 2014; 20:957-67. [PMID: 24574768 PMCID: PMC3921547 DOI: 10.3748/wjg.v20.i4.957] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2013] [Revised: 12/05/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
In recent years, the need to identify molecular markers characterized by high sensitivity and specificity in detecting and monitoring early and colorectal cancer lesions has increased. Up to now, none of the markers or panels of markers analyzed have met the rigorous standards required of a screening program. The important discovery of circulating nucleic acids in biological fluids has aroused intense scientific interest because of their usefulness in malignant and non malignant diseases. Over time, their yield and stability have been identified and compared with other "standard" biomarkers. The analysis of circulating DNA from blood and stool is a relatively simple and non-invasive procedure, representing a very attractive marker to detect genetic and epigenetic mutations and to monitor disease progression. A correlation between blood and stool biomarkers could also help to enhance currently available diagnostic approaches. However, various processing and analytic problems need to be resolved before such an approach can be applied in clinical practice.
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Kim SB, Min YH, Cheong JW, Kim JS, Kim SJ, Ku NS, Jeong SJ, Han SH, Choi JY, Song YG, Kim JM. Incidence and risk factors for carbapenem- and multidrug-resistant Acinetobacter baumannii bacteremia in hematopoietic stem cell transplantation recipients. ACTA ACUST UNITED AC 2013; 46:81-8. [DOI: 10.3109/00365548.2013.857042] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Marchesi F, Mengarelli A, Giannotti F, Tendas A, Anaclerico B, Porrini R, Picardi A, Cerchiara E, Dentamaro T, Chierichini A, Romeo A, Cudillo L, Montefusco E, Tirindelli MC, De Fabritiis P, Annino L, Petti MC, Monarca B, Arcese W, Avvisati G. High incidence of post-transplant cytomegalovirus reactivations in myeloma patients undergoing autologous stem cell transplantation after treatment with bortezomib-based regimens: a survey from the Rome transplant network. Transpl Infect Dis 2013; 16:158-64. [PMID: 24215479 DOI: 10.1111/tid.12162] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Revised: 04/19/2013] [Accepted: 05/13/2013] [Indexed: 01/13/2023]
Abstract
The incidence of cytomegalovirus (CMV) reactivations in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT) is relatively low. However, the recent increased use of novel agents, such as bortezomib and/or immunomodulators, before transplant, has led to an increasing incidence of Herpesviridae family virus infections. The aim of the study was to establish the incidence of post-engraftment symptomatic CMV reactivations in MM patients receiving ASCT, and to compare this incidence with that of patients treated with novel agents or with conventional chemotherapy before transplant. The study was a survey of 80 consecutive patients who underwent ASCT after treatment with novel agents (Group A). These patients were compared with a cohort of 89 patients treated with VAD regimen (vincristine, doxorubicin, and dexamethasone) before ASCT (Group B). Overall, 7 patients (4.1%) received an antiviral treatment for a symptomatic CMV reactivation and 1 died. The incidence of CMV reactivations was significantly higher in Group A than in Group B (7.5% vs. 1.1%; P = 0.048). When compared with Group B, the CMV reactivations observed in Group A were significantly more frequent in patients who received bortezomib, whether or not associated with immunomodulators (9.4% vs. 1.1%; P = 0.019), but not in those treated with immunomodulators only (3.7% vs. 1.1%; P = 0.396). These results suggest that MM patients treated with bortezomib-based regimens are at higher risk of developing a symptomatic CMV reactivation after ASCT.
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Affiliation(s)
- F Marchesi
- Hematology Unit, Campus Bio-Medico University Hospital, Rome, Italy
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Kowalsky S, Arnon R, Posada R. Prevention of cytomegalovirus following solid organ transplantation: a literature review. Pediatr Transplant 2013; 17:499-509. [PMID: 23890075 DOI: 10.1111/petr.12118] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/29/2013] [Indexed: 02/06/2023]
Abstract
CMV is the most common opportunistic infection affecting SOT recipients. Although current strategies to prevent both CMV infection and disease have been effective, CMV related complications continue to occur, particularly late-onset CMV disease. This literature review article examines the benefits and disadvantages of different prevention modalities, and presents emerging strategies to better prevent CMV in organ transplant recipients.
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Affiliation(s)
- Shanna Kowalsky
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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Coisel Y, Bousbia S, Forel JM, Hraiech S, Lascola B, Roch A, Zandotti C, Million M, Jaber S, Raoult D, Papazian L. Cytomegalovirus and herpes simplex virus effect on the prognosis of mechanically ventilated patients suspected to have ventilator-associated pneumonia. PLoS One 2012; 7:e51340. [PMID: 23236477 PMCID: PMC3517464 DOI: 10.1371/journal.pone.0051340] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2012] [Accepted: 11/07/2012] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE Cytomegalovirus (CMV) and herpes simplex virus (HSV) are common viruses that can affect critically ill patients who are not immunocompromised. The aim of this study was to determine whether the identification of CMV and/or HSV in mechanically ventilated critically ill patients suspected of having pneumonia was associated with an increased mortality. DESIGN Prospective epidemiological study. SETTING Medical intensive care unit of a tertiary medical center. PATIENTS Ninety-three patients with suspected pneumonia. INTERVENTIONS Patients with suspected pneumonia had bronchoalveolar lavage and blood samples taken to confirm the diagnosis. Antigenemia was used to detect CMV in the blood. Bronchoalveolar lavage samples were submitted to testing using quantitative real-time Polymerase Chain Reaction. MEASUREMENTS AND MAIN RESULTS We identified 22 patients with a CMV infection, 26 patients with an HSV infection and 45 patients without CMV or HSV infection (control group). Mortality at day 60 was higher in patients with a CMV infection than in patients from the control group (55% vs. 20%, P<0.01). Mortality at day 60 was not significantly increased in the group with HSV infection. Duration of ICU stay and ICU mortality were significantly higher in patients with CMV infections when compared to patients from the control group, whereas ventilator free days were significantly lower in patients with CMV infections when compared to patients from the control group. CONCLUSIONS In critically ill patients, a CMV infection is associated with an increased mortality. Further interventional studies are needed to evaluate whether treatment could improve the prognosis.
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Affiliation(s)
- Yannael Coisel
- Service d'Anesthésie-Réanimation Saint Eloi, Centre Hospitalier Universitaire, and INSERM Unité 1046, Université Montpellier 1, Montpellier, France.
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Schlischewsky E, Fuehner T, Warnecke G, Welte T, Haverich A, Ganzenmueller T, Heim A, Gottlieb J. Clinical significance of quantitative cytomegalovirus detection in bronchoalveolar lavage fluid in lung transplant recipients. Transpl Infect Dis 2012; 15:60-9. [DOI: 10.1111/tid.12015] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2011] [Revised: 06/02/2012] [Accepted: 06/14/2012] [Indexed: 12/21/2022]
Affiliation(s)
- E. Schlischewsky
- Department of Respiratory Medicine; Hannover Medical School; Hannover; Germany
| | - T. Fuehner
- Department of Respiratory Medicine; Hannover Medical School; Hannover; Germany
| | - G. Warnecke
- Department of Cardiothoracic, Transplant and Vascular Surgery; Hannover Medical School; Hannover; Germany
| | - T. Welte
- Department of Respiratory Medicine; Hannover Medical School; Hannover; Germany
| | - A. Haverich
- Department of Cardiothoracic, Transplant and Vascular Surgery; Hannover Medical School; Hannover; Germany
| | - T. Ganzenmueller
- Institute of Virology; Hannover Medical School; Hannover; Germany
| | - A. Heim
- Institute of Virology; Hannover Medical School; Hannover; Germany
| | - J. Gottlieb
- Department of Respiratory Medicine; Hannover Medical School; Hannover; Germany
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Verheyen J, Kaiser R, Bozic M, Timmen-Wego M, Maier BK, Kessler HH. Extraction of viral nucleic acids: Comparison of five automated nucleic acid extraction platforms. J Clin Virol 2012; 54:255-9. [DOI: 10.1016/j.jcv.2012.03.008] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2011] [Revised: 03/13/2012] [Accepted: 03/14/2012] [Indexed: 02/02/2023]
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Wiita A, Roubinian N, Khan Y, Chin-Hong P, Singer J, Golden J, Miller S. Cytomegalovirus disease and infection in lung transplant recipients in the setting of planned indefinite valganciclovir prophylaxis. Transpl Infect Dis 2012; 14:248-58. [DOI: 10.1111/j.1399-3062.2012.00723.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2011] [Revised: 10/18/2011] [Accepted: 12/08/2011] [Indexed: 11/28/2022]
Affiliation(s)
- A.P. Wiita
- Department of Laboratory Medicine; University of California; San Francisco; California; USA
| | - N. Roubinian
- Division of Pulmonary and Critical Care; Department of Medicine; University of California; San Francisco; California; USA
| | - Y. Khan
- Clinical Microbiology Laboratory; University of California; San Francisco; California; USA
| | - P.V. Chin-Hong
- Division of Infectious Diseases; Department of Medicine; University of California; San Francisco; California; USA
| | - J.P. Singer
- Division of Pulmonary and Critical Care; Department of Medicine; University of California; San Francisco; California; USA
| | - J.A. Golden
- Division of Pulmonary and Critical Care; Department of Medicine; University of California; San Francisco; California; USA
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Spieler P, Rössle M. Respiratory Tract and Mediastinum. ESSENTIALS OF DIAGNOSTIC PATHOLOGY 2012. [PMCID: PMC7122295 DOI: 10.1007/978-3-642-24719-4_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Normal cytology, abnormal and atypical cells, non-cellular components, and infectious cell changes are largely described together with benign, malignant, and neuroendocrine lesions regarding exfoliative and aspiration cytology of the lung. A separate section broadly addresses diagnostic findings and differential diagnoses in bronchoalveolar washings. The section ‘Fine needle aspiration biopsy of mediastinal disorders’ covers in particular biopsy techniques, accuracy of liquid-based cytology, and the complex lesions of the thymus gland. Cytodiagnostic algorithms of the major benign and malignant pulmonary and mediastinal lesions and their respective differential diagnoses are additionally presented in synoptic setups.
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Affiliation(s)
- Peter Spieler
- Institut für Pathologie, Kantonsspital St. Gallen, Rorschacherstraße 95, 9007 St. Gallen, Switzerland
| | - Matthias Rössle
- Institut für Klinische Pathologie, UniversitätsSpital Zürich, Schmelzbergstraße 12, 8091 Zürich, Switzerland
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Laboratory Diagnosis of Infection Due to Viruses, Chlamydia, Chlamydophila, and Mycoplasma. PRINCIPLES AND PRACTICE OF PEDIATRIC INFECTIOUS DISEASES 2012. [PMCID: PMC7152074 DOI: 10.1016/b978-1-4377-2702-9.00289-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Genotyping cytomegalovirus UL97 mutations by high-resolution melting analysis with unlabeled probe. Arch Virol 2011; 157:475-81. [PMID: 22205145 DOI: 10.1007/s00705-011-1173-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2011] [Accepted: 11/08/2011] [Indexed: 10/14/2022]
Abstract
Human cytomegalovirus (CMV) is an opportunistic pathogen, and infections with this virus can be treated with ganciclovir (GCV). Most GCV-resistant clinical CMV isolates contain a mutation in the UL97 gene. Genotypic assays for diagnostic screening of GCV-resistant CMV have been developed. High-resolution melting analysis (HRMA) with unlabeled probe is considered a perfect tool for this purpose. In this study, we have developed an HRMA-based genotypic test for the detection of UL97 mutations. Wild type and M460V/I mutants of UL97 were constructed. HRMA with unlabeled probe was used as a genotyping method for the detection of M460V/I mutations. The melting peaks obtained directly from PCR products did not enable us to distinguish the wild type from M460 mutants. The sensitivity and accuracy of HRMA were dramatically improved by using unlabeled probe. HRMA with unlabeled probe successfully distinguished M460V from M460I and served well for the detection of M460V/I mutations in clinical samples. HRMA with unlabeled probe proves to be a sensitive and cost-effective genotyping method for the detection of M460 mutations.
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Tachikawa R, Tomii K, Ueda H, Nagata K, Nanjo S, Sakurai A, Otsuka K, Kaji R, Hayashi M, Katakami N, Imai Y. Clinical features and outcome of acute exacerbation of interstitial pneumonia: collagen vascular diseases-related versus idiopathic. ACTA ACUST UNITED AC 2011; 83:20-7. [PMID: 21912082 DOI: 10.1159/000329893] [Citation(s) in RCA: 100] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2011] [Accepted: 06/07/2011] [Indexed: 11/19/2022]
Abstract
BACKGROUND Relatively little is known about acute exacerbation (AE) of interstitial pneumonia associated with collagen vascular diseases (CVD-IPs). OBJECTIVES This study was aimed at clarifying clinical characteristics and outcome in AE of CVD-IPs, compared with those of idiopathic interstitial pneumonias (IIPs). METHODS We retrospectively reviewed 112 admission cases with suspected AE of CVD-IPs or IIPs during 2003-2009. IIPs were diagnosed with idiopathic pulmonary fibrosis (IPF) or non-IPF, mostly based on radiologic findings. Of these, 15 AEs of CVD-IPs (6 rheumatoid arthritis, 6 dermatomyositis and 3 systemic sclerosis) and 47 AEs of IIPs (13 IPF and 34 non-IPF) were included. RESULTS The clinical characteristics in AE of CVD-IPs were similar to those of IIPs, except for younger age (63.3 ± 6.8 vs. 73.8 ± 9.1 years; p = 0.0001) and higher PaO(2)/FiO(2) at the onset of AE (205 ± 81.2 vs. 145 ± 53.8 mm Hg; p = 0.002) in the former. Dermatomyositis-related interstitial pneumonia (IP) showed a relatively indolent onset and was often associated with worsening control of the underlying disease, whereas AE of other CVD-IPs resembled that of IIPs. 90-day mortality of 33% in AE of CVD-IPs was similar to that of IIPs (44%; p = 0.44) or non-IPF (34%; p = 0.94), but was significantly better than that of IPF (69%; p = 0.04). CONCLUSION Clinical features and outcome in AE of CVD-IPs were similar, if not identical, to those of IIPs, having a significant impact on the clinical course. AE of advanced IPF with typical radiologic features seems to have higher mortality compared with other forms of IP.
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Affiliation(s)
- Ryo Tachikawa
- Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
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Feasey NA, Healey P, Gordon MA. Review article: the aetiology, investigation and management of diarrhoea in the HIV-positive patient. Aliment Pharmacol Ther 2011; 34:587-603. [PMID: 21777262 DOI: 10.1111/j.1365-2036.2011.04781.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Diarrhoea is a common presentation throughout the course of HIV disease. AIM To review the literature relating to aetiology, investigation and management of diarrhoea in the HIV-infected adult. METHODS The PubMed database was searched using major subject headings 'AIDS' or 'HIV' and 'diarrhoea' or 'intestinal parasite'. The search was limited to adults and to studies with >10 patients. RESULTS Diarrhoea affects 40-80% of HIV-infected adults untreated with antiretroviral therapy (ART). First-line investigation is by stool microbiology. Reported yield varies with geography and methodology. Molecular and immunological methods and special stains have improved diagnostic yield. Endoscopy is diagnostic in 30-70% of cases of pathogen-negative diarrhoea and evidence supports flexible sigmoidoscopy as a first line screening procedure (80-95% sensitive for CMV colitis), followed by colonoscopy and terminal ileoscopy. Radiology is useful to assess severity, distribution, complications and to diagnose HIV-related malignancies. Side effects and compliance with ART are important considerations in assessment. There is a good evidence base for many specific therapies, but optimal treatment of cryptosporidiosis is unclear and only limited data support symptomatic treatments. CONCLUSIONS The immunological response to HIV infection and Antiretroviral therapy remains incompletely understood. Antiretroviral therapy regimens need to be optimised to suppress HIV while minimising side effects. Effective agents for management of cryptosporidiosis are lacking. There is an urgent need for enhanced regional diagnostic facilities in countries with a high prevalence of HIV. The ongoing roll-out of Antiretroviral therapy in low-resource settings will continue to change the aetiology and management of this problem, necessitating ongoing surveillance and study.
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Affiliation(s)
- N A Feasey
- Department of Gastroenterology, University of Liverpool, Liverpool, UK
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33
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Mead R, Duku M, Bhandari P, Cree IA. Circulating tumour markers can define patients with normal colons, benign polyps, and cancers. Br J Cancer 2011; 105:239-45. [PMID: 21712823 PMCID: PMC3142810 DOI: 10.1038/bjc.2011.230] [Citation(s) in RCA: 101] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background: Early diagnosis represents the best opportunity for cure of colorectal cancer. Current screening programmes use faecal occult blood testing for screening, which has limited sensitivity and poor specificity. Methods: In this study we looked at a series of previously described diagnostic markers utilising circulating free DNA (cfDNA), with a preparation method allowing small DNA fragments to be isolated. The Circulating free DNA was isolated from samples obtained from 85 patients, including 35 patients without endoscopic abnormality, a group of 26 patients with benign colorectal adenomas, and 24 patients with colorectal carcinomas. In each case, polymerase chain reaction (PCR) was performed for Line1 79 bp, Line1 300 bp, Alu 115 bp, Alu 247 bp, and mitochondrial primers. In addition, carcinoembryonic antigen (CEA) was measured by ELISA. Each marker was analysed between normal, polyp, and cancer populations, and the best performing analysed in combination by logistic regression. Results: The best model was able to discriminate normal from populations with adenoma or carcinoma using three DNA markers and CEA, showing an area under the receiver operator characteristic (ROC) curve of 0.855 with a positive predictive value of 81.1% for polyps and cancer diagnosis. Conclusion: These circulating markers in combination with other markers offer the prospect of a simple blood test as a possible secondary screen for colorectal cancers and polyps in patients with positive faecal occult blood tests.
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Affiliation(s)
- R Mead
- Department of Gastroenterology and Translational Oncology Research Centre, Queen Alexandra Hospital, Portsmouth PO6 3LY, UK
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Prevalence and outcome of cytomegalovirus-associated pneumonia in relation to human immunodeficiency virus infection. Pediatr Infect Dis J 2011; 30:413-7. [PMID: 21150691 DOI: 10.1097/inf.0b013e3182065197] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
AIM To investigate the antemortem prevalence and outcome of cytomegalovirus (CMV)-associated pneumonia in African children. METHODS A total of 202 children (median age, 3.2 months; 124 human immunodeficiency virus [HIV]-infected, 62%; 87 severely malnourished, 43%) sequentially hospitalized for severe pneumonia were prospectively investigated. In addition to routine microbiologic investigations, respiratory tract secretions and blood were submitted for CMV culture and qualitative and quantitative CMV polymerase chain reaction. RESULTS CMV-associated pneumonia was common (28%, 47/169) and more prevalent in HIV-infected than uninfected children (36% vs. 15%; odds ratio [OR], 3.0; 95% confidence interval, 1.3-7.4). CMV-associated pneumonia was more common than Pneumocystis pneumonia (27%) and other viral-associated pneumonia (19%) in HIV-infected children. In-hospital mortality was 25% (51/202) with increased mortality in HIV-infected compared with uninfected children (43/124 [35%] vs. 8/76 [11%]; OR, 4.5; 1.9-11.8). Increased mortality occurred in HIV-infected children with CMV-associated pneumonia (OR, 2.5; 1.04-6.5) but this association was not evident after adjusting for CD4 <15% (adjusted OR, 1.78; 0.6-4.6). CONCLUSIONS CMV-associated pneumonia is common and associated with a poor outcome in children with advanced HIV disease. Improved diagnostic testing and increased access to antiviral therapy might improve the outcome of HIV-infected children with CMV-associated pneumonia.
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Burrows SR, Moss DJ, Khanna R. Understanding human T-cell-mediated immunoregulation through herpesviruses. Immunol Cell Biol 2011; 89:352-8. [PMID: 21301481 DOI: 10.1038/icb.2010.136] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Human herpesviruses have coevolved with humans over millions of years, and adaptation of latent infection within the cells of the immune system is a unique characteristic of many of these viruses. Following primary infection, these herpesviruses establish an asymptomatic-persistent infection in healthy individuals that is strictly controlled by virus-specific CD8(+) and CD4(+) T cells. Here, we provide a brief overview of how the human immune system interacts with these latent viruses and regulates the lifelong host-virus relationship in healthy virus carriers. Extensive studies on T-cell-mediated immune regulation over the last decade has allowed researchers to successfully translate these findings into the clinical setting to treat various herpesvirus-associated diseases in transplant patients and individuals with virus-associated malignancies. It is highly likely that these newly emerging T-cell-based therapeutic and diagnostic technologies will revolutionize the clinical management of patients with herpesvirus-associated diseases.
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Affiliation(s)
- Scott R Burrows
- Australian Centre for Vaccine Development, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
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38
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Chiavarini M, Bragetti P, Sensini A, Cenci E, Castronari R, Rossi MJ, Fantauzzi A, Minelli L. Breastfeeding and transmission of cytomegalovirus to preterm infants. Case report and kinetic of CMV-DNA in breast milk. Ital J Pediatr 2011; 37:6. [PMID: 21247481 PMCID: PMC3032676 DOI: 10.1186/1824-7288-37-6] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2010] [Accepted: 01/19/2011] [Indexed: 11/10/2022] Open
Abstract
Background Breastfeeding has a major impact on CMV epidemiology. Postnatal CMV reactivation's incidence during lactation is nearby the maternal seroprevalence. Although perinatal CMV infection has practically no consequences in term newborn, it may cause, in some cases, a severe symptomatic disease in preterm newborns. The aims of the present study are to evaluate the rate and clinical expression of CMV infection breast milk transmitted in preterm infants and to check the safety of the freezing treated breast milk. Methods The study included fifty-seven preterm infants and their CMV seropositive mothers. Fresh breast milk samples have been collected from 1st to 9th postpartum week. Both fresh breast milk and 72, 96, 120 hours frozen samples have been examined, checking the presence of CMV; urine samples have been tested too. Results 70.2% of tested mothers showed reactivation of the infection, and CMV-positive breast milk during the six weeks postpartum has been found. However, only one infant was infected by CMV, developing hepatic affection concomitantly with a multi-system involvement, as shown CMV DNA detection in urine, saliva, blood, gastric aspirate, and stools. Conclusion Freezing breast milk at -20°C and pasteurization may respectively reduce or eliminate the viral load.
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Affiliation(s)
- Manuela Chiavarini
- Department of Medical and Surgical Specialities and Public Health, Public Health section, University of Perugia School of Medicine, Italy
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Kim DH, Na YS, Lee HJ, Kim YS, Kim HS. A Case of Cytomegalovirus Infection Presenting as Pericarditis and Lupus Nephritis Flare-up. JOURNAL OF RHEUMATIC DISEASES 2011. [DOI: 10.4078/jrd.2011.18.3.224] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Dong-Hyun Kim
- Department of Internal Medicine, The Chosun University College of Medicine, Gwangju, Korea
| | - Yong-Sub Na
- Department of Internal Medicine, The Chosun University College of Medicine, Gwangju, Korea
| | - Hee-Jeong Lee
- Department of Internal Medicine, The Chosun University College of Medicine, Gwangju, Korea
| | - Yun Sung Kim
- Department of Internal Medicine, The Chosun University College of Medicine, Gwangju, Korea
| | - Hyun-Sook Kim
- Department of Internal Medicine, The Chosun University College of Medicine, Gwangju, Korea
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40
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AIDS Patients in the ICU. INFECTION CONTROL IN THE INTENSIVE CARE UNIT 2011. [PMCID: PMC7120342 DOI: 10.1007/978-88-470-1601-9_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
At the beginning of the AIDS epidemic, there were higher mortality rates in patients requiring admission to an intensive care unit (ICU) most likely due to acute respiratory failure. Whereas the use of prophylaxis and corticosteroids for Pneumocystisjiroveci pneumonia and highly active antiretroviral therapy has changed this outcome and has improved survival rate. However, respiratory failure has remained the most common indication for an ICU admission. When HIV-infected patients are admitted to the ICU, intensivists need to be knowledgeable about the manifestations of common diseases and the new manifestations related to antiretroviral therapy. Much HIV mortality has been linked directly to late diagnosis and late initiation of appropriate antiviral therapy. This l, the most important cause of ICU admission for AIDS patients. We analyzed the characteristics of P.jiroveci pneumonia, bacterial pneumonia, cytomegalovirus pneumonia, mycobacterial infections, pulmonary invasive fungal infections, Kaposi’s sarcoma, and the immune reconstitution inflammatory syndrome.
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De la Cruz-Vicente F, Perez-Romero P, Aguilar-Guisado M, Cisneros-Herreros JM, Urbano-Ispizua A, Espigado I. Clinical utility of real-time polymerase chain reaction to quantify cytomegalovirus replication in allogeneic stem cell transplant recipients with different prevention strategies. Transplant Proc 2010; 42:3228-9. [PMID: 20970660 DOI: 10.1016/j.transproceed.2010.05.050] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Cytomegalovirus (CMV) end-organ disease is a serious, frequent complication after allogenic stem cell transplantation (Allo-SCT). There are two prevention strategies: universal prophylaxis and preemptive therapy. Preemptive therapy is administered based on the results of sensitive techniques that detect the viral infection. We analyzed 41 peripheral blood Allo-SCT recipients: 34 received prophylaxis and seven preemptive treatment. Viral infections determined using real-time polymerase chain reaction (RT-PCR) assays occurred at an overall incidence of 65.8%. The viral loads quantified by RT-PCR were compared among the prophylaxis versus the preemptive group. Overall, the median viral load was significantly higher in the preemptive compared with the prophylaxis group (P=.002). Furthermore, within the first 100 days posttransplantation, viral load values were higher among patients undergoing preemptive therapy (P=.009).
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Affiliation(s)
- F De la Cruz-Vicente
- Hematology and Hemotherapy Department, Hospital Universitario Virgen del Rocío, Seville, Spain.
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42
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Ticha O, Stouracova M, Kuman M, Studenik P, Freiberger T, Litzman J. Monitoring of CD38high expression in peripheral blood CD8+ lymphocytes in patients after kidney transplantation as a marker of cytomegalovirus infection. Transpl Immunol 2010; 24:50-6. [DOI: 10.1016/j.trim.2010.10.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2010] [Revised: 09/30/2010] [Accepted: 10/05/2010] [Indexed: 10/18/2022]
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Batalla AS, Benito D, Baumard S, Brodard V, Servettaz A, Jaussaud R, Strady C. [Epstein-Barr virus and cytomegalovirus primary infections: a comparative study in 52 immunocompetent adults]. Med Mal Infect 2010; 41:14-9. [PMID: 20832213 DOI: 10.1016/j.medmal.2010.07.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2009] [Revised: 06/15/2010] [Accepted: 07/26/2010] [Indexed: 11/18/2022]
Abstract
OBJECTIVE The objective of this study was to compare epidemiological, clinical, and biological data of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) primary infections in immunocompetent adults, admitted in the infectious disease department of the Reims Teaching Hospital between 2000 and 2005. PATIENTS AND METHODS Inclusion criteria were the presence of anti-VCA IgM antibodies or the presence of CMV specific IgM antibodies and the absence of any other positive serology. Differences in reported percentage were compared with a Khi(2) test or Fischer's exact test, when appropriate. Continuous variables were compared with the Mann-Whitney Test. RESULTS There were no significant changes over the years in the numbers of EBV (n=32) and CMV (n=20) primary infections. The patient's mean age was 22.7 years (14-48 years) in EBV primary infections and 38.6 years (13-66 years) in CMV primary infections (P<0.01). The clinical variables significantly associated with primary EBV infection were sore throat and cervical lymphadenopathy (P<0.01). Arthromyalgia and respiratory manifestations were less frequent in EBV primary infection (P<0.01). The biological variables significantly associated with EBV primary infection were a marked alanine aminotransferase elevation and a marked lymphocytosis with atypical lymphocytes (P<0.001). Thrombopenia was less frequently associated with EBV primary infection (P<0.001). CONCLUSION Clinical and biological presentations of EBV and CMV primary infections were similar. The simultaneous serologic diagnosis of these two infections remains necessary to provide a specific diagnosis, for the most efficient patient care.
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Affiliation(s)
- A-S Batalla
- Service de médecine interne et des maladies infectieuses, hôpital Robert-Debré, avenue du Général-Koenig, Reims cedex, France
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Eisenstein EM, Wolf DG. Cytomegalovirus infection in pediatric rheumatic diseases: a review. Pediatr Rheumatol Online J 2010; 8:17. [PMID: 20487534 PMCID: PMC2885386 DOI: 10.1186/1546-0096-8-17] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2009] [Accepted: 05/20/2010] [Indexed: 11/28/2022] Open
Abstract
Human cytomegalovirus (HCMV) is familiar to pediatric rheumatologists mainly as a cause of opportunistic disease in pharmacologically immune suppressed patients. However, HCMV also has a variety of immuno-modulatory effects, through which it may influence the course of rheumatic conditions. In this article we discuss the interplay between HCMV and the immune system, and review the clinical manifestations, diagnosis, and treatment of HCMV infection in children with rheumatic disease.
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Affiliation(s)
- Eli M Eisenstein
- Department of Pediatrics, Hadassah-Hebrew University Medical Center, POB 24035, Mount Scopus, Jerusalem 91240, Israel.
| | - Dana G Wolf
- Department of Clinical Microbiology & Infectious Diseases, Hadassah-Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel
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Ridha E, Cookson H, Devitt E, Nelson M. Febrile neutropenia in a HIV positive individual post-chemotherapy. J Clin Virol 2010; 48:2-5. [PMID: 20171139 DOI: 10.1016/j.jcv.2010.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2010] [Revised: 01/09/2010] [Accepted: 01/13/2010] [Indexed: 11/25/2022]
Affiliation(s)
- E Ridha
- Department of HIV Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.
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Chevillotte M, von Einem J, Meier BM, Lin FM, Kestler HA, Mertens T. A new tool linking human cytomegalovirus drug resistance mutations to resistance phenotypes. Antiviral Res 2010; 85:318-27. [DOI: 10.1016/j.antiviral.2009.10.004] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2009] [Revised: 10/02/2009] [Accepted: 10/10/2009] [Indexed: 11/25/2022]
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Kim YC, Kim GM, Lee HS, Hong SI, Cheung DY, Kim JI, Park SH, Kim JK. A Case of Hemophagocytic Syndrome in an Ulcerative Colitis Patient. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2010; 56:45-8. [DOI: 10.4166/kjg.2010.56.1.45] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- Yong Cheol Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Gun Min Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Ho Sang Lee
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Seok In Hong
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Dae Young Cheung
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jin Il Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Soo-Heon Park
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jae Kwang Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
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Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, Wingard JR, Young JAH, Boeckh MJ, Boeckh MA. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 2009; 15:1143-238. [PMID: 19747629 PMCID: PMC3103296 DOI: 10.1016/j.bbmt.2009.06.019] [Citation(s) in RCA: 1195] [Impact Index Per Article: 74.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2009] [Accepted: 06/23/2009] [Indexed: 02/07/2023]
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50
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Zaravinos A, Bizakis J, Spandidos DA. Prevalence of human papilloma virus and human herpes virus types 1-7 in human nasal polyposis. J Med Virol 2009; 81:1613-9. [PMID: 19626617 DOI: 10.1002/jmv.21534] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
This study aimed to investigate the prevalence of human papilloma virus (HPV), herpes simplex virus-1/-2 (HSV-1/-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6/-7 (HHV-6/-7) in 23 human nasal polyps by applying PCR. Two types of control tissues were used: adjacent inferior/middle turbinates from the patients and inferior/middle turbinates from 13 patients undergoing nasal corrective surgery. EBV was the virus most frequently detected (35%), followed by HPV (13%), HSV-1 (9%), and CMV (4%). The CMV-positive polyp was simultaneously positive for HSV-1. HPV was also detected in the adjacent turbinates (4%) and the adjacent middle turbinate (4%) of one of the HPV-positive patients. EBV, HSV, and CMV were not detected in the adjacent turbinates of the EBV-, HSV- or CMV-positive patients. All mucosae were negative for the VZV, HHV-6, and HHV-7. This is the first study to deal with the involvement of a comparable group of viruses in human nasal polyposis. The findings support the theory that the presence of viral EBV markedly influences the pathogenesis of these benign nasal tumors. The low incidence of HPV detected confirms the hypothesis that HPV is correlated with infectious mucosal lesions to a lesser extent than it is with proliferative lesions, such as inverted papilloma. The low incidence of HSV-1 and CMV confirms that these two herpes viruses may play a minor role in the development of nasal polyposis. Double infection with HSV-1 and CMV may also play a minor, though causative, role in nasal polyp development. VZV and HHV-6/-7 do not appear to be involved in the pathogenesis of these mucosal lesions.
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Affiliation(s)
- Apostolos Zaravinos
- Laboratory of Virology, Medical School, University of Crete, Heraklion, Crete, Greece
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