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Biology of Blood and Marrow... Oct 2018Over the past 25 years, several randomized controlled trials have investigated the efficacy of different antiviral agents for cytomegalovirus (CMV) prophylaxis in... (Comparative Study)
Comparative Study Meta-Analysis
Comparative Efficacy and Safety of Different Antiviral Agents for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplantation: A Systematic Review and Meta-Analysis.
Over the past 25 years, several randomized controlled trials have investigated the efficacy of different antiviral agents for cytomegalovirus (CMV) prophylaxis in allogeneic hematopoietic cell transplantation. We performed a systematic literature review, conventional meta-analysis, and network meta-analysis using a random-effects model and risk ratios (RRs) with corresponding 95% confidence intervals (CIs) as effect estimates. Fifteen randomized controlled trials were identified, including 7 different antiviral agents: acyclovir, ganciclovir, maribavir, brincidofovir, letermovir, valacyclovir, and vaccine. Twelve trials used placebo as comparator while 3 trials compared different antiviral agents. We found evidence for CMV disease and infection being significantly reduced by antiviral prophylaxis, with an RR of .66 (95% CI, .48 to .90) and .63 (95% CI, .50 to .79). Across the network, ganciclovir showed the best relative efficacy for CMV disease while letermovir provided first rank of being the best option for CMV infection. The risk for death was not significantly influenced by antiviral prophylaxis in the meta-analysis, with an RR of .92 (95% CI, .78 to 1.08), as well as in the network meta-analysis. In terms of safety, letermovir was at least similar in comparison with placebo and most agents while both letermovir and acyclovir showed significantly reduced risk for serious adverse events compared with ganciclovir, with RRs of .55 (95% CI, .30 to 1.00) for letermovir and .63 (95% CI, .42 to .93) for acyclovir. With a probability of 81%, letermovir appears to be the best option in terms of safety. Future randomized head-to-head comparisons are needed to evaluate the definite efficacy and safety of different prophylactic strategies.
Topics: Acetates; Acyclovir; Allografts; Antiviral Agents; Benzimidazoles; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Male; Quinazolines; Ribonucleosides; Risk Factors; Valacyclovir
PubMed: 29777868
DOI: 10.1016/j.bbmt.2018.05.017 -
Journal of Cutaneous Medicine and... 2023Human herpesvirus-6 (HHV-6) is a ubiquitous lymphotropic betaherpesvirus that can reactivate in drug rash with eosinophilia and systemic symptoms (DRESS). Despite recent... (Review)
Review
INTRODUCTION
Human herpesvirus-6 (HHV-6) is a ubiquitous lymphotropic betaherpesvirus that can reactivate in drug rash with eosinophilia and systemic symptoms (DRESS). Despite recent publications advancing our understanding of HHV-6 in DRESS, the exact role of HHV-6 in disease pathogenesis remains unclear.
METHODS
A scoping review with the PubMed query "(HHV 6 AND (drug OR DRESS OR DIHS)) OR (HHV6 AND (drug OR DRESS OR DIHS))" was conducted in accordance with PRISMA guidelines. Articles containing original data on at least one DRESS patient with HHV-6 testing were included.
RESULTS
Our search returned a total of 373 publications, of which 89 met eligibility criteria. HHV-6 reactivation occurred in 63% of DRESS patients (n = 748), which was significantly more often than other herpesviruses. HHV-6 reactivation was associated with worse outcomes and greater severity in controlled studies. Case reports have demonstrated sometimes fatal HHV-6-related multi-organ involvement. Temporally, HHV-6 reactivation typically occurs 2 to 4 weeks after DRESS onset and has been linked to markers of immunologic signaling, such as OX40 (CD134), an HHV-6 entry receptor. Efficacy of antiviral or immunoglobulin treatment has only been demonstrated anecdotally, and steroid use may affect HHV-6 reactivation.
CONCLUSION
HHV-6 is implicated in DRESS more than in any other dermatologic condition. It is still unclear whether HHV-6 reactivation is cause or consequence of DRESS dysregulation. Similar pathogenic mechanisms precipitated by HHV-6 in other contexts may be relevant in DRESS. Future randomized controlled studies to assess effects of viral suppression on clinical outcomes is needed.
Topics: Humans; Herpesvirus 6, Human; Eosinophilia; Drug Eruptions; Exanthema
PubMed: 37231539
DOI: 10.1177/12034754231177590 -
PloS One 2019Despite considerable research, it remains controversial as to whether viral-infections are associated with Meniere's Disease (MD), a clinically heterogeneous set of... (Meta-Analysis)
Meta-Analysis
Are viral-infections associated with Ménière's Disease? A systematic review and meta-analysis of molecular-markers of viral-infection in case-controlled observational studies of MD.
Despite considerable research, it remains controversial as to whether viral-infections are associated with Meniere's Disease (MD), a clinically heterogeneous set of chronic inner-ear disorders strongly associated with endolymphatic hydrops. Here, we investigated whether viral-infections are associated with MD through a systematic review and meta-analysis of observational clinical studies using molecular-diagnostics. Eligible for inclusion were case-controlled studies which ascertained molecular-determinants of past or present viral-infection through either viral nucleic acids or host serological marker in MD cases and non-MD controls. Across online databases and grey literature, we identified 210 potentially relevant articles in the English language, from which a total of 14 articles fully satisfied our eligibility criteria such that meta-groups of 611 MD-cases and 373 controls resulted. The aggregate quality of the modest-sized (14 studies) body of evidence was limited and varied considerably with regards to participant selection, matching, and ascertainment(s) and determinant(s) of viral-infection. Most data identified concerned the human cytomegalovirus (CMV), and meta-analysis of eligible studies revealed that evidence of CMV-infection was associated approximately three-fold with MD compared to controls, however the timing of the infections was indeterminate as the pooled analyses combined antiviral serological markers with viral nucleic acid markers. No association was found for any of HSV-1, -2, VZV, or EBV. Associative analyses of any viral species not aforementioned were precluded by limited data, and thus potential associations between other viral species and MD, especially other than Herpesviridae, are yet to be characterised. Overall, we have found a small association between CMV-infection and MD, however it is to be determined for what sub-groups of MD this finding may be relevant, and ideally the reported association remains would be reproduced by a greater volume of higher quality evidence.
Topics: Antibodies, Viral; Cytomegalovirus; DNA, Viral; Databases, Factual; Humans; Meniere Disease; Observational Studies as Topic; Odds Ratio; Virus Diseases
PubMed: 31756230
DOI: 10.1371/journal.pone.0225650 -
International Journal of Infectious... May 2023Herpesviruses are ubiquitous and after primary infection they establish lifelong latency. The impairment of maintaining latency with short-term or long-term consequences... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Herpesviruses are ubiquitous and after primary infection they establish lifelong latency. The impairment of maintaining latency with short-term or long-term consequences could be triggered by other infection. Therefore, reactivation of herpesviruses in COVID-19 patients represents an emerging issue.
DESIGN AND METHODS
This study provided the first systematic review with meta-analysis of studies that evaluated active human herpesvirus (HHV) infection (defined as the presence of IgM antibodies or HHV-DNA) in COVID-19 patients and included 36 publications collected by searching through PubMed, SCOPUS, and Web of science until November 2022.
RESULTS
The prevalence of active EBV, HHV6, HSV, CMV, HSV1, and VZV infection in COVID-19 population was 41% (95% CI =27%-57%), 3% (95% CI=17%-54%), 28% (95% CI=1%-85%), 25% (95% CI=1%-63%), 22% (95% CI=10%-35%), and 18% (95% CI=4%-34%), respectively. There was a 6 times higher chance for active EBV infection in patients with severe COVID-19 than in non-COVID-19 controls (OR=6.45, 95% CI=1.09-38.13, p=0.040), although there was no difference in the prevalence of all evaluated active herpesvirus infections between COVID-19 patients and non-COVID-19 controls.
CONCLUSIONS
Future research of herpesvirus and SARS-CoV-2 coinfections must be prioritized to define: who, when and how to be tested, as well as how to effectively treat HHVs reactivations in acute and long COVID-19 patients.
Topics: Humans; Post-Acute COVID-19 Syndrome; Herpesvirus 4, Human; Cytomegalovirus; COVID-19; SARS-CoV-2; Herpesviridae Infections; Herpesviridae; Simplexvirus; Herpesvirus 6, Human
PubMed: 36736577
DOI: 10.1016/j.ijid.2023.01.036 -
Biology of Blood and Marrow... Nov 2018Graft-versus-host disease (GVHD) is an important cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Many studies have suggested... (Meta-Analysis)
Meta-Analysis
Human Herpesvirus-6B Reactivation Is a Risk Factor for Grades II to IV Acute Graft-versus-Host Disease after Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.
Graft-versus-host disease (GVHD) is an important cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Many studies have suggested that human herpesvirus-6B (HHV-6B) plays a role in acute GVHD (aGVHD) after HCT. Our objective was to systematically summarize and analyze evidence regarding HHV-6B reactivation and development of aGVHD. PubMed and EMBASE databases were searched using terms for HHV-6, HCT, and aGVHD, yielding 865 unique results. Case reports, reviews, articles focusing on inherited chromosomally integrated HHV-6, poster presentations, and articles not published in English were excluded. The remaining 467 articles were reviewed for the following requirements: a statistical analysis of HHV-6B reactivation and aGVHD was described, HHV-6B reactivation was defined by PCR, and blood (plasma, serum, or peripheral blood mononuclear cells) was used for HHV-6B PCR. Data were abstracted from publications that met these criteria (n = 33). Publications were assigned to 1 of 3 groups: (1) HHV-6B reactivation was analyzed as a time-dependent risk factor for subsequent aGVHD (n = 14), (2) aGVHD was analyzed as a time-dependent risk factor for subsequent HHV-6B reactivation (n = 1), and (3) analysis without temporal specification (n = 18). A statistically significant association (P < .05) between HHV-6B reactivation and aGVHD was observed in 10 of 14 studies (71%) in group 1, 0 of 1 study (0%) in Group 2, and 8 of 18 studies (44.4%) in Group 3. Of the 14 studies that analyzed HHV-6B as a risk factor for subsequent aGVHD, 11 performed a multivariate analysis and reported a hazard ratio, which reached statistical significance in 9 of these studies. Meta-analysis of these 11 studies demonstrated a statistically significant association between HHV-6B and subsequent grades II to IV aGVHD (hazard ratio, 2.65; 95% confidence interval, 1.89 to 3.72; P < .001). HHV-6B reactivation is associated with aGVHD, and when studies have a temporal component to their design, HHV-6B reactivation is associated with subsequent aGVHD. Further research is needed to investigate whether antiviral prophylaxis reduces incidence or severity of aGVHD.
Topics: Acute Disease; Adolescent; Adult; Aged; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Herpesvirus 6, Human; Humans; Male; Middle Aged; Neoplasm Grading; Risk Factors; Transplantation Conditioning; Young Adult
PubMed: 29684567
DOI: 10.1016/j.bbmt.2018.04.021 -
Medical Microbiology and Immunology Aug 2019Latent infection with cytomegalovirus (CMV) is thought to accelerate aging of the immune system. With age, influenza vaccine responses are impaired. Although several... (Meta-Analysis)
Meta-Analysis
Latent infection with cytomegalovirus (CMV) is thought to accelerate aging of the immune system. With age, influenza vaccine responses are impaired. Although several studies investigated the effect of CMV infection on antibody responses to influenza vaccination, this led to contradicting conclusions. Therefore, we investigated the relation between CMV infection and the antibody response to influenza vaccination by performing a systematic review and meta-analysis. All studies on the antibody response to influenza vaccination in association with CMV infection were included (n = 17). The following outcome variables were extracted: (a) the geometric mean titer pre-/post-vaccination ratio (GMR) per CMV serostatus group, and in addition (b) the percentage of subjects with a response per CMV serostatus group and (c) the association between influenza- and CMV-specific antibody titers. The influenza-specific GMR revealed no clear evidence for an effect of CMV seropositivity on the influenza vaccine response in young or old individuals. Meta-analysis of the response rate to influenza vaccination showed a non-significant trend towards a negative effect of CMV seropositivity. However, funnel plot analysis suggests that this is a consequence of publication bias. A weak negative association between CMV antibody titers and influenza antibody titers was reported in several studies, but associations could not be analyzed systematically due to the variety of outcome variables. In conclusion, by systematically integrating the available studies, we show that there is no unequivocal evidence that latent CMV infection affects the influenza antibody response to vaccination. Further studies, including the level of CMV antibodies, are required to settle on the potential influence of latent CMV infection on the influenza vaccine response.
Topics: Antibodies, Viral; Antibody Formation; Cytomegalovirus; Cytomegalovirus Infections; Humans; Immunosenescence; Influenza Vaccines; Orthomyxoviridae; Virus Latency
PubMed: 30949763
DOI: 10.1007/s00430-019-00602-z -
Revista Espanola de Quimioterapia :... Feb 2023To determine the prevalence of CMV reactivation in a population admitted for severe COVID-19 to a general hospital.
OBJECTIVE
To determine the prevalence of CMV reactivation in a population admitted for severe COVID-19 to a general hospital.
METHODS
Point prevalence study in all hospitalized patients with severe COVID-19 (admitted either to general wards or ICU). Determination of the presence of CMV DNA in circulating blood. COVID-19 was confirmed in patients with compatible clinical manifestations, usually with pneumonia and a positive nasopharyngeal PCR test.
RESULTS
We included 140 hospitalized patients with COVID-19 who consented to participate. A total of 16 patients (11.42%), had circulating CMV-DNA in peripheral blood at the time of the study. Patients with positive CMV viral load were mainly ICU patients (11/37 -29,7%) and only 5/103 cases (4,85%) were hospitalized into general wards. The accumulated doses of corticosteroids (prednisone equivalents) in the study day were (median and IQR) 987.50 mg (396.87-2,454.68) and 187.50 mg (75.00-818.12) respectively in CMV positive and negative patients (p < 0.001). A significant proportion of CMV positive patients were discovered because of the study and were clinically unsuspected by their physicians. The coinfected COVID-CMV positive population had a higher risk of accumulated secondary nosocomially-acquired infections and a worse prognosis.
CONCLUSIONS
CMV reactivation should be systematically searched in patients in COVID-19 cases admitted to the ICU.
Topics: Humans; Cytomegalovirus Infections; Cytomegalovirus; Prevalence; COVID-19; Hospitals, General
PubMed: 36408974
DOI: 10.37201/req/068.2022 -
Medicine Oct 2019To evaluate if splenectomy results in severely impaired immune responses against primary cytomegalovirus (CMV) infection compared to the general immunocompetent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate if splenectomy results in severely impaired immune responses against primary cytomegalovirus (CMV) infection compared to the general immunocompetent population.
METHODS
We performed a systemic literature review to study CMV infections in splenectomized individuals, a special population group presently considered immunocompetent to viral infections. We retrieved 30 cases with established CMV infection post-splenectomy and we recorded their disease manifestations, laboratory findings, immunological studies, and histopathology reports. In addition, we retrieved numerous multidisciplinary articles in view of post-splenectomy immunology defects, as well as of immune responses to primary invading CMV in the absence of the spleen. Two clinical studies directly comparing splenectomized with nonsplenectomized individuals under severe iatrogenic immunosuppression as well as the numerically largest review articles of CMV infections in immunocompetent were retained.
RESULTS
Splenectomy results in the loss of spleen's ability to fend-off blood-borne pathogens and impairs the link between innate and adaptive immunity. The major post-splenectomy immune-defects against CMV are: weakened, delayed or absent anti-CMV IgM, and compensatory marked IgG response; severely impaired B-cell and CD4, CD8 T-cells function responses; and post-splenectomy, bone marrow compensates for the absence of spleen's immune responses against CMV, mimicking a monoclonal T-cell lymphoproliferative process.
CONCLUSION
The puzzled diagnosis of the CMV syndrome post-splenectomy is of the most challenging and misleading, resulting in risky and costly interventions and a subsequent prolonged hospitalization (2 months). The mounting multi-disciplinary literature evidence renders us to suggest that splenectomized individuals are not only prone to encapsulated bacteria but also behave as immunocompromised to CMV.
Topics: Cytomegalovirus; Cytomegalovirus Infections; Humans; Immunocompromised Host; Splenectomy
PubMed: 31651900
DOI: 10.1097/MD.0000000000017698 -
BMC Pregnancy and Childbirth Feb 2024Human Cytomegalovirus (HCMV) is the most frequent congenital infection worldwide causing important sequelae. However, no vaccine or antiviral treatments are currently...
BACKGROUND
Human Cytomegalovirus (HCMV) is the most frequent congenital infection worldwide causing important sequelae. However, no vaccine or antiviral treatments are currently available, thus interventions are restricted to behavioral measures. The aim of this systematic review was to assess evidence from available intervention studies using hygiene-based measures to prevent HCMV infection during pregnancy.
METHODS
Studies published from 1972 to 2023 were searched in Medline, PsycInfo, and Clinical Trials (PROSPERO, CRD42022344840) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality was assessed by two authors, using ROBE-2 and MINORS.
RESULTS
After reviewing 6 selected articles, the outcome analysis suggested that implementation of hygiene-based interventions during pregnancy prevent, to some extent, the acquisition of congenital HCMV.
CONCLUSIONS
However, these conclusions are based on limited and low-quality evidence available from few studies using this type of intervention in clinical practice. Thus, it would be necessary to perform effective and homogeneous intervention studies using hygiene-based measures, evaluated in high-quality randomized controlled trials (RCTs).
Topics: Female; Humans; Pregnancy; Cytomegalovirus; Cytomegalovirus Infections; Hygiene; Pregnancy Complications, Infectious
PubMed: 38424481
DOI: 10.1186/s12884-024-06367-5 -
Acta Neurologica Taiwanica Mar 2021Encephalitis secondary to human herpesvirus 6 (HHV-6) infection is frequently encountered in immunocompromised patients; in contrast, HHV-6 encephalitis in...
PURPOSE
Encephalitis secondary to human herpesvirus 6 (HHV-6) infection is frequently encountered in immunocompromised patients; in contrast, HHV-6 encephalitis in immunocompetent patients is rare. There are only 3 reports of status epilepticus due to HHV-6 encephalitis in immunocompetent adults. In the present study, a case of refractory status epilepticus secondary to HHV-6 encephalitis was reported in an immunocompetent female.
CASE REPORT
We report a case of a previously healthy 46-year-old female who presented with a one-week history of back pain, fever and generalized tonic-clonic seizures that progressed to status epilepticus. The video electroencephalography showed epileptiform discharges on both frontotemporal regions. Neuroimaging showed hyperintensities on the bilateral insula and temporal lobes. The cerebrospinal fluid showed elevated pressure and was positive for HHV-6. She was given ganciclovir and a total of eleven antiepileptic drugs. Despite these medications, she developed refractory status epilepticus and eventually succumbed due to multiple medical complications.
CONCLUSION
This case highlights HHV-6 encephalitis as an important diagnostic consideration in patients presenting with refractory status epilepticus, regardless of immune status.
Topics: Adult; Female; Humans; Middle Aged; Anticonvulsants; Encephalitis; Encephalitis, Viral; Herpesvirus 6, Human; Status Epilepticus
PubMed: 34549397
DOI: No ID Found