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Microbiology Spectrum Aug 2016Cytomegalovirus (CMV), the largest of the herpesviruses, causes a wide range of clinical syndromes, from asymptomatic infection to severe disease in immunocompromised... (Review)
Review
Cytomegalovirus (CMV), the largest of the herpesviruses, causes a wide range of clinical syndromes, from asymptomatic infection to severe disease in immunocompromised hosts. Laboratory methods for diagnosis include molecular testing, antigenemia, culture, serology, and histopathology. Treatment of CMV infection and disease is indicated in selected immunocompromised hosts, and preventive approaches are indicated in high-risk groups. This chapter reviews the epidemiology, clinical aspects, and the laboratory diagnosis and management of CMV in immunocompromised hosts.
Topics: Antiviral Agents; Clinical Laboratory Techniques; Cytomegalovirus; Cytomegalovirus Infections; Diagnostic Tests, Routine; Disease Susceptibility; Humans; Immunocompromised Host
PubMed: 27726793
DOI: 10.1128/microbiolspec.DMIH2-0022-2015 -
Clinical Microbiology and Infection :... Jan 2023The burden that cytomegalovirus (CMV) portends for haematopoietic and solid-organ transplant recipients cannot be understated. Valganciclovir and ganciclovir have... (Review)
Review
BACKGROUND
The burden that cytomegalovirus (CMV) portends for haematopoietic and solid-organ transplant recipients cannot be understated. Valganciclovir and ganciclovir have successfully been used for prevention and treatment of CMV infections, although with serious side effects such as leucopenia and some development of resistance. Until recently, available therapies for ganciclovir-resistant CMV have significant toxicities. Although advances have been made in the field, the unmet medical needs for effective and well-tolerated therapies are significant.
OBJECTIVES
This review aims to summarise the current and emerging CMV antiviral drugs and discusses future perspectives in the field.
SOURCES
We searched for relevant articles with pertinent keywords: "Cytomegalovirus OR CMV", "Transplant" and "Antiviral". Articles published after 2019 were given preference. Articles were reviewed by the authors for relevance and impact to the subject of interest.
CONTENT
We outline in this review current advances in prophylaxis of CMV infection with letermovir, breakthrough CMV infections while on or after prophylaxis, the development of resistant and refractory CMV infections, and the newly approved anti-CMV agent, maribavir, in haematopoietic and solid-organ transplant recipients.
IMPLICATIONS
Prevention of CMV infections after transplant has improved greatly over the past few years. Despite major advancements, breakthrough CMV infections and development of refractory and resistant CMV infections remain major complications post transplantation. We highlight emerging therapeutics that tolerably and effectively prevent and treat CMV infections, especially refractory and resistant cases.
Topics: Humans; Transplant Recipients; Cytomegalovirus Infections; Antiviral Agents; Ganciclovir; Cytomegalovirus
PubMed: 35843567
DOI: 10.1016/j.cmi.2022.07.001 -
The Journal of Infectious Diseases Mar 2020Congenital cytomegalovirus (cCMV) infection is a leading cause of hearing loss and neurological disabilities in children, with the disease burden and disabilities due to... (Review)
Review
Congenital cytomegalovirus (cCMV) infection is a leading cause of hearing loss and neurological disabilities in children, with the disease burden and disabilities due to cCMV greater than many other well recognized childhood conditions. A minority of infants with cCMV will have symptoms at birth. Infants with symptomatic cCMV are at higher risk for sequelae than those born without symptoms. The majority of infants with cCMV are asymptomatic at birth, but 10%-15% will develop hearing loss. Although clinical symptoms can help predict which infants will have sensorineural hearing loss, among asymptomatic cCMV there are currently no predictors of adverse outcome. The identification of a biomarker to identify those at highest risk of sequelae is highly desirable to target interventions to those who could potentially benefit. Because there is increasing rationale for establishing both targeted and universal screening programs for cCMV in the United States and worldwide, this is an urgent priority.
Topics: Child; Cytomegalovirus; Cytomegalovirus Infections; Disabled Persons; Female; Hearing Loss, Sensorineural; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Neonatal Screening; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Symptom Assessment
PubMed: 32134480
DOI: 10.1093/infdis/jiz446 -
American Journal of Transplantation :... Feb 2013Cytomegalovirus (CMV) is the most common infection after organ transplantation and has a major impact on morbidity, mortality and graft survival. Optimal prevention,... (Review)
Review
Cytomegalovirus (CMV) is the most common infection after organ transplantation and has a major impact on morbidity, mortality and graft survival. Optimal prevention, diagnosis and treatment of active CMV infection enhance transplant outcomes, and are the focus of this section. Methods to prevent CMV include universal prophylaxis and preemptive therapy; each has its merits, and will be compared and contrasted. Diagnostics have improved substantially in recent years, both in type and quality, allowing for more accurate and savvy treatment; advances in diagnostics include the development of an international standard, which should allow comparison of results across different methodologies, and assays for cellular immune function against CMV. Therapy primarily involves ganciclovir, now rendered more versatile by data suggesting oral therapy with valganciclovir is not inferior to intravenous therapy with ganciclovir. Treatment of resistant virus remains problematic, but is enhanced by the availability of multiple novel therapeutic agents.
Topics: Administration, Oral; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Resistance, Viral; Ganciclovir; Graft Survival; Humans; Organ Transplantation; Valganciclovir
PubMed: 23347212
DOI: 10.1111/ajt.12006 -
Dermatology Online Journal Jan 2019The possible presentations of cytomegalovirus (CMV) are vast not only in its systemic manifestations, but also in the various cutaneous lesions that may result.... (Review)
Review
The possible presentations of cytomegalovirus (CMV) are vast not only in its systemic manifestations, but also in the various cutaneous lesions that may result. Cutaneous cytomegalovirus is rarely reported in the literature because the clinical and pathologic features can be difficult to identify. Its identification, however, is vital as cutaneous human CMV infection can signal systemic disease and an unfavorable prognosis. The objective of this study is to aid in recognition, diagnosis, and treatment of CMV according to dermatological evidence. A complete literature search was performed within PubMed, resulting in the inclusion of 58 patient cases. The most common dermatologic manifestation was perianal or oral ulcers, but the locations and types of lesions noted throughout the review were numerous. Treatment is often simple, yet incorrect diagnoses along with concurrent illnesses can often complicate management. It is imperative for CMV to be detected early in its course to prevent mortality, especially in the immunocompromised. Dermatological presentations are often the first sign of this deadly virus' activity and it is essential that these diagnoses are made more efficient and accurate.
Topics: Antiviral Agents; Cytomegalovirus Infections; HIV Infections; Humans; Immunocompromised Host; Immunosuppressive Agents; Organ Transplantation; Skin Diseases, Viral
PubMed: 30710895
DOI: No ID Found -
Birth Defects Research Mar 2017Cytomegalovirus (CMV) is a DNA herpesvirus that is common worldwide. The two known main sources of primary CMV infection during pregnancy are through sexual activity and... (Review)
Review
Cytomegalovirus (CMV) is a DNA herpesvirus that is common worldwide. The two known main sources of primary CMV infection during pregnancy are through sexual activity and contact with young children. Primary infection occurs in approximately 1 to 4% of pregnancies, and is mostly asymptomatic in immunocompetent adults. However, primary infection may manifest as a mild mononucleosis or flu-like syndrome with persistent fever and fatigue. CMV can be transmitted from mother-to-child in utero, intrapartum, or during breastfeeding. Intrauterine transmission can lead to congenital CMV infection, a leading cause of permanent hearing and vision loss and neurological disability among children. Congenital CMV transmission rates are as high as 50% in women who acquire primary CMV infection during pregnancy, and less than 2% in women with nonprimary infection. There is no licensed CMV vaccine. Good hygiene practices and avoiding intimate contact with young children (e.g., kissing on the mouth and sharing utensils) have been suggested as an approach to prevent maternal primary CMV infection during pregnancy, but remains an unproven method of reducing the risk of congenital CMV infection. Approximately 1 in 10 infants who acquire CMV in utero will have clinical signs at birth, and an additional 10 to 15% will go on to develop late-onset sequelae. Antiviral treatment prenatally and postnatally has not proven effective at preventing congenital or postnatal CMV infection, and is not recommended for routine clinical care. However, antiviral treatment when initiated in the first month of life for symptomatic congenital CMV infection is recommended for improved neurodevelopmental and audiologic outcomes. Birth Defects Research 109:336-346, 2017. © 2017 Wiley Periodicals, Inc.
Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Hygiene; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Prenatal Exposure Delayed Effects
PubMed: 28398680
DOI: 10.1002/bdra.23601 -
The Journal of Infectious Diseases Mar 2020This review focuses on recent advances in the field of cytomegalovirus (CMV). The 2 main strategies for CMV prevention are prophylaxis and preemptive therapy.... (Review)
Review
This review focuses on recent advances in the field of cytomegalovirus (CMV). The 2 main strategies for CMV prevention are prophylaxis and preemptive therapy. Prophylaxis effectively prevents CMV infection after solid organ transplantation (SOT) but is associated with high rates of neutropenia and delayed-onset postprophylaxis disease. In contrast, preemptive therapy has the advantage of leading to lower rates of CMV disease and robust humoral and T-cell responses. It is widely used in hematopoietic cell transplant recipients but is infrequently utilized after SOT due to logistical considerations, though these may be overcome by novel methods to monitor CMV viremia using self-testing platforms. We review recent developments in CMV immune monitoring, vaccination, and monoclonal antibodies, all of which have the potential to become part of integrated strategies that rely on viral load monitoring and immune responses. We discuss novel therapeutic options for drug-resistant or refractory CMV infection, including maribavir, letermovir, and adoptive T-cell transfer. We also explore the role of donor factors in transmitting CMV after SOT. Finally, we propose a framework with which to approach CMV prevention in the foreseeable future.
Topics: Antiviral Agents; Clinical Decision-Making; Cytomegalovirus; Cytomegalovirus Infections; Disease Management; Disease Susceptibility; Hematopoietic Stem Cell Transplantation; Humans; Neutropenia; Organ Transplantation; Pre-Exposure Prophylaxis; Time Factors; Tissue Donors; Transplant Recipients; Viral Vaccines
PubMed: 32134486
DOI: 10.1093/infdis/jiz454 -
Clinical Microbiology Reviews Dec 2020Hosts with compromised or naive immune systems, such as individuals living with HIV/AIDS, transplant recipients, and fetuses, are at the highest risk for complications... (Review)
Review
Hosts with compromised or naive immune systems, such as individuals living with HIV/AIDS, transplant recipients, and fetuses, are at the highest risk for complications from cytomegalovirus (CMV) infection. Despite substantial progress in prevention, diagnostics, and treatment, CMV continues to negatively impact both solid-organ transplant (SOT) and hematologic cell transplant (HCT) recipients. In this article, we summarize important developments in the field over the past 10 years and highlight new approaches and remaining challenges to the optimal control of CMV infection and disease in transplant settings.
Topics: Antiviral Agents; Clinical Trials as Topic; Cytomegalovirus Infections; Early Diagnosis; Humans; Immunocompromised Host; Organ Transplantation
PubMed: 33115722
DOI: 10.1128/CMR.00043-19 -
Transplant Infectious Disease : An... Dec 2022The CMV Symposium in September 2021 was an international conference dedicated to cytomegalovirus (CMV) infection after solid organ or hematopoietic stem cell... (Review)
Review
The CMV Symposium in September 2021 was an international conference dedicated to cytomegalovirus (CMV) infection after solid organ or hematopoietic stem cell transplantation. This review provides an overview of the presentations given by the expert faculty, supplemented with educational clinical cases. Topics discussed include CMV epidemiology and diagnosis, the burden of CMV infection and disease, CMV-specific immunity and management of CMV in transplant settings. Major advances in the prevention and treatment of CMV in the past decade and increased understanding of CMV immunity have led to improved patient outcomes. In the future, management algorithms may be individualized based on the transplant recipient's immune profile, which will mark the start of a new era for patients with CMV.
Topics: Humans; Cytomegalovirus; Cytomegalovirus Infections; Organ Transplantation; Lung Transplantation; Hematopoietic Stem Cell Transplantation; Antiviral Agents
PubMed: 36271650
DOI: 10.1111/tid.13977 -
Italian Journal of Pediatrics Apr 2017Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide, with an estimated incidence in developing countries of 0.6-0.7% of all live births.... (Review)
Review
Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide, with an estimated incidence in developing countries of 0.6-0.7% of all live births. The burden of disease related to congenital CMV in substantial, as it is the leading non-genetic cause of sensorineural hearing loss and an important cause of neurodevelopmental disabilities in children. Despite its clinical significance, congenital CMV infection often goes undetected because the majority of infected infants are asymptomatic at birth and screening programs have not been substantially implemented. Other than behavioral measures, effective interventions aimed at the prevention of maternal infection and of mother-to-child transmission are lacking. Due to a convergence of recent advances in both diagnostic and therapeutic strategies in infants with congenital CMV, though, the field likely will be changing rapidly over just the next few years. Specifically, a highly-sensitive screening test with high throughput potential has been developed, and treatment of infants symptomatically infected with congenital CMV has proven to be well-tolerated and effective in improving long-term hearing and neurodevelopmental outcomes.This review highlights the clinical importance of congenital CMV infection, the developments in laboratory diagnostics, and the benefits of antiviral therapy. It also identifies the global efforts still required in the prevention of maternal infection and in the optimization of antiviral therapy to further reduce the burden of congenital CMV disease.
Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Developing Countries; Early Diagnosis; Female; Humans; Incidence; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Pregnancy; Pregnancy Complications, Infectious; Risk Assessment; Severity of Illness Index; Survival Rate
PubMed: 28416012
DOI: 10.1186/s13052-017-0358-8