Severe fetal symptomatic infection from human cytomegalovirus following non-primary maternal infection: report of two cases

2021 ◽  
Author(s):  
Mariano Matteo Lanna ◽  
Elisa Fabbri ◽  
Maurizio Zavattoni ◽  
Chiara Doneda ◽  
Valentina Toto ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Fetal Brain ◽  
Cortical Plate ◽  
Maternal Infection ◽  
Cerebral Lesions ◽  
Morphological Pattern ◽  
First Case ◽  
Hcmv Disease ◽  
The Impact

Introduction Human cytomegalovirus (HCMV) is the most common congenital infection, expecially severe after a maternal primary infection; sequelae in neonates born to mothers experiencing a non-primary infection have been already reported. Hereby, two cases of severe fetal HCMV disease in seroimmune gravidas referred to our Unit are described. Cases presentation Case 1 A fetus at 21 weeks’ gestation with signs of anemia and brain abnormalities at ultrasound (US), described at magnetic resonance (MR) imaging as ependymal irregularity and bilateral asymmetric parenchimal thinning; amniotic fluid sample was positive for HCMV although the woman had a previous immunity; after termination of pregnancy, autopsy demonstrated a thicken layer of disorganized neurons on the right cortical plate, while on the left there was a morphological pattern coherent with polymicrogyria. Case 2 A fetus at 20 weeks’ gestation with anemia, moderate atrio-ventricular insufficiency, hepatosplenomegaly but no major cerebral lesions. Fetal blood was positive for HCMV, although unexpected for pre-pregnancy maternal immunity, and intrauterine transfusion was needed. A cesarean section at 34 weeks gestation was performed due to worsening condition of the fetus, who had a birthweight of 2210 grams, needed platelet transfusions but MR examination and clinical evaluation were normal. Conclusion The impact of non-primary maternal infection on pregnancy outcome is unknown and fetal brain damage in HCMV seroimmune transmitter-mothers can occur as a consequence of maternal re-infection or reactivation for a hypotetic different role of HCMV-primed CD4+ or CD8+ T-cells in fetal brain, with progressive brain lesions coexistent in the first case and with severe unexpected anemia in the second case. A previous maternal HCMV immunity should not exempt to test anemic fetuses for such infection, nor to consider a potential transplacental transmission.

scholarly journals Diagnosis and Management of Human Cytomegalovirus Infection in the Mother, Fetus, and Newborn Infant

2002 ◽  
Vol 15 (4) ◽  
pp. 680-715 ◽  
Author(s):  
Maria Grazia Revello ◽  
Giuseppe Gerna
Keyword(s):  
Prenatal Diagnosis ◽  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Hcmv Infection ◽  
Prognostic Markers ◽  
Recurrent Infection ◽  
Congenital Infection ◽  
Immunoglobulin M ◽  
Hcmv Disease ◽  
The Impact

SUMMARY Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection and mental retardation. HCMV infection, while causing asymptomatic infections in most immunocompetent subjects, can be transmitted during pregnancy from the mother with primary (and also recurrent) infection to the fetus. Hence, careful diagnosis of primary infection is required in the pregnant woman based on the most sensitive serologic assays (immunoglobulin M [IgM] and IgG avidity assays) and conventional virologic and molecular procedures for virus detection in blood. Maternal prognostic markers of fetal infection are still under investigation. If primary infection is diagnosed in a timely manner, prenatal diagnosis can be offered, including the search for virus and virus components in fetal blood and amniotic fluid, with fetal prognostic markers of HCMV disease still to be defined. However, the final step for definite diagnosis of congenital HCMV infection is detection of virus in the blood or urine in the first 1 to 2 weeks of life. To date, treatment of congenital infection with antiviral drugs is only palliative both prior to and after birth, whereas the only efficacious preventive measure seems to be the development of a safe and immunogenic vaccine, including recombinant, subunit, DNA, and peptide-based vaccines now under investigation. The following controversial issues are discussed in the light of the most recent advances in the field: the actual perception of the problem; universal serologic screening before pregnancy; the impact of correct counseling on decision making by the couple involved; the role of prenatal diagnosis in ascertaining transmission of virus to the fetus; the impact of preconceptional and periconceptional infections on the prevalence of congenital infection; and the prevalence of congenitally infected babies born to mothers who were immune prior to pregnancy compared to the number born to mothers undergoing primary infection during pregnancy.

scholarly journals HCMV Antivirals and Strategies to Target the Latent Reservoir

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 817
Author(s):  
Marianne R. Perera ◽  
Mark R. Wills ◽  
John H. Sinclair
Keyword(s):  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Latent Infection ◽  
Severe Disease ◽  
Unmet Need ◽  
Human Herpesvirus ◽  
Viral Resistance ◽  
Latent Reservoir ◽  
Transplant Recipients ◽  
Hcmv Disease

Human cytomegalovirus (HCMV) is a ubiquitous human herpesvirus. In healthy people, primary infection is generally asymptomatic, and the virus can go on to establish lifelong latency in cells of the myeloid lineage. However, HCMV often causes severe disease in the immunosuppressed: transplant recipients and people living with AIDS, and also in the immunonaive foetus. At present, there are several antiviral drugs licensed to control HCMV disease. However, these are all faced with problems of poor bioavailability, toxicity and rapidly emerging viral resistance. Furthermore, none of them are capable of fully clearing the virus from the host, as they do not target latent infection. Consequently, reactivation from latency is a significant source of disease, and there remains an unmet need for treatments that also target latent infection. This review briefly summarises the most common HCMV antivirals used in clinic at present and discusses current research into targeting the latent HCMV reservoir.

Impact of hydroxychloroquin/azithromycin protocol on COVID-19 case-fatality rate reduction in Algeria. (Preprint)

2020 ◽  
Author(s):  
Ahmed Youssef Kada
Keyword(s):  
Case Fatality Rate ◽  
Doubling Time ◽  
Case Fatality ◽  
World Health ◽  
Fatality Rate ◽  
Therapeutic Protocol ◽  
First Case ◽  
The World ◽  
The Impact ◽  
At Home

BACKGROUND Covid-19 is an emerging infectious disease like viral zoonosis caused by new coronavirus SARS CoV 2. On December 31, 2019, Wuhan Municipal Health Commission in Hubei province (China) reported cases of pneumonia, the origin of which is a new coronavirus. Rapidly extendable around the world, the World Health Organization (WHO) declares it pandemic on March 11, 2020. This pandemic reaches Algeria on February 25, 2020, date on which the Algerian minister of health, announced the first case of Covid-19, a foreign citizen. From March 1, a cluster is formed in Blida and becomes the epicentre of the coronavirus epidemic in Algeria, its total quarantine is established on March 24, 2020, it will be smoothly alleviated on April 24. A therapeutic protocol based on hydroxychloroquine and azithromycin was put in place on March 23, for complicated cases, it was extended to all the cases confirmed on April 06. OBJECTIVE This study aimed to demonstrate the effectiveness of hydroxychloroquin/azithromycin protocol in Algeria, in particular after its extension to all patients diagnosed COVID-19 positive on RT-PCR test. We were able to illustrate this fact graphically, but not to prove it statistically because the design of our study, indeed in the 7 days which followed generalization of therapeutic protocol, case fatality rate decrease and doubling time increase, thus confirming the impact of wide and early prescription of hydroxychloroquin/azithromycin protocol. METHODS We have analyzed the data collected from press releases and follow-ups published daily by the Ministry of Health, we have studied the possible correlations of these data with certain events or decisions having a possible impact on their development, such as confinement at home and its reduction, the prescription of hydroxychloroquine/azithromycin combination for serious patients and its extension to all positive COVID subjects. Results are presented in graphics, the data collection was closed on 31/05/2020. RESULTS Covid-19 pandemic spreads from February 25, 2020, when a foreign citizen is tested positive, on March 1 a cluster is formed in the city of Blida where sixteen members of the same family are infected during a wedding party. Wilaya of Blida becomes the epicentre of coronavirus epidemic in Algeria and lockdown measures taken, while the number of national cases diagnosed begins to increases In any event, the association of early containment measures combined with a generalized initial treatment for all positive cases, whatever their degree of severity, will have contributed to a reduction in the fatality rate of COVID 19 and a slowing down of its doubling time. CONCLUSIONS In Algeria, the rapid combination of rigorous containment measure at home and early generalized treatment with hydroxychloroquin have demonstrated their effectiveness in terms of morbidity and mortality, the classic measures of social distancing and hygiene will make it possible to perpetuate these results by reducing viral transmission, the only unknown, the reopening procedure which can only be started after being surrounded by precautions aimed at ensuring the understanding of the population. CLINICALTRIAL Algeria, Covid-19, pandemic, hydroxychloroquin, azithromycin, case fatality rate

scholarly journals Histone H3 Lysine 4 Methylation Marks Postreplicative Human Cytomegalovirus Chromatin

2012 ◽  
Vol 86 (18) ◽  
pp. 9817-9827 ◽  
Author(s):  
Alexandra Nitzsche ◽  
Charlotte Steinhäußer ◽  
Katrin Mücke ◽  
Christina Paulus ◽  
Michael Nevels
Keyword(s):  
Dna Replication ◽  
Dna Synthesis ◽  
Histone Modification ◽  
Dna Polymerase ◽  
Human Cytomegalovirus ◽  
Viral Genome ◽  
Histone H3 ◽  
Viral Dna ◽  
The Impact ◽  
Preferential Incorporation

In the nuclei of permissive cells, human cytomegalovirus genomes form nucleosomal structures initially resembling heterochromatin but gradually switching to a euchromatin-like state. This switch is characterized by a decrease in histone H3 K9 methylation and a marked increase in H3 tail acetylation and H3 K4 methylation across the viral genome. We used ganciclovir and a mutant virus encoding a reversibly destabilized DNA polymerase to examine the impact of DNA replication on histone modification dynamics at the viral chromatin. The changes in H3 tail acetylation and H3 K9 methylation proceeded in a DNA replication-independent fashion. In contrast, the increase in H3 K4 methylation proved to depend widely on viral DNA synthesis. Consistently, labeling of nascent DNA using “click chemistry” revealed preferential incorporation of methylated H3 K4 into viral (but not cellular) chromatin during or following DNA replication. This study demonstrates largely selective epigenetic tagging of postreplicative human cytomegalovirus chromatin.

scholarly journals The Effects of Maternal Interleukin-17A on Social Behavior, Cognitive Function, and Depression-Like Behavior in Mice with Altered Kynurenine Metabolites

2021 ◽  
Vol 14 ◽  
pp. 117864692110266
Author(s):  
Yuki Murakami ◽  
Yukio Imamura ◽  
Yoshiyuki Kasahara ◽  
Chihiro Yoshida ◽  
Yuta Momono ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Fetal Brain ◽  
Autism Spectrum ◽  
Maternal Serum ◽  
Fetal Plasma ◽  
Maternal Inflammation ◽  
Interleukin 17A ◽  
Behavioral Abnormalities ◽  
Neuroactive Compounds ◽  
The Impact

Viral infection and chronic maternal inflammation during pregnancy are correlated with a higher prevalence of autism spectrum disorder (ASD). However, the pathoetiology of ASD is not fully understood; moreover, the key molecules that can cross the placenta following maternal inflammation and contribute to the development of ASD have not been identified. Recently, the pro-inflammatory cytokine, interleukin-17A (IL-17A) was identified as a potential mediator of these effects. To investigate the impact of maternal IL-17A on offspring, C57BL/6J dams were injected with IL-17A-expressing plasmids via the tail vein on embryonic day 12.5 (E12.5), and maternal IL-17A was expressed continuously throughout pregnancy. By adulthood, IL-17A-injected offspring exhibited behavioral abnormalities, including social and cognitive defects. Additionally, maternal IL-17A promoted metabolism of the essential amino acid tryptophan, which produces several neuroactive compounds and may affect fetal neurodevelopment. We observed significantly increased levels of kynurenine in maternal serum and fetal plasma. Thus, we investigated the effects of high maternal concentration of kynurenine on offspring by continuously administering mouse dams with kynurenine from E12.5 during gestation. Obviously, maternal kynurenine administration rapidly increased kynurenine levels in the fetal plasma and brain, pointing to the ability of kynurenine to cross the placenta and change the KP metabolites which are affected as neuroactive compounds in the fetal brain. Notably, the offspring of kynurenine-injected mice exhibited behavioral abnormalities similar to those observed in offspring of IL-17A-conditioned mice. Several tryptophan metabolites were significantly altered in the prefrontal cortex of the IL-17A-conditioned and kynurenine-injected adult mice, but not in the hippocampus. Even though we cannot exclude the possibility or other molecules being related to ASD pathogenesis and the presence of a much lower degree of pathway activation, our results suggest that increased kynurenine following maternal inflammation may be a key factor in changing the balance of KP metabolites in fetal brain during neuronal development and represents a therapeutic target for inflammation-induced ASD-like phenotypes.

scholarly journals A Case of COVID-19-Related Thrombocytopenia and Leukopenia in an Adolescent with Mild Symptoms

Children ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 509
Author(s):  
Lydia Kossiva ◽  
Athanasios Thirios ◽  
Eleni Panagouli ◽  
Alexandros Panos ◽  
Stavroula Lampidi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Viral Infection ◽  
Nasal Congestion ◽  
Pediatric Population ◽  
Clinical Manifestations ◽  
Bone Marrow Aspiration ◽  
White Blood Count ◽  
Chronic Obstructive ◽  
First Case ◽  
The Impact

Since the beginning of the COVID-19 pandemic, there have been numerous reports and reviews on the complications caused by the disease, analyzing the acute and chronic consequences. The main symptoms of SARS-CoV-2 are dry cough, fever, and fatigue. COVID-19 appears to affect all systems, including renal, cardiovascular, circulatory, and respiratory systems, causing chronic obstructive pulmonary disease. We report on a 14-year-old male adolescent, who presented with thrombocytopenia (platelet count 92 × 109 /L) and leukopenia (white blood count 4.2 × 103 /μL) that was observed two months ago. Ten days before the first blood test, a viral infection with nasal congestion and runny nose was reported, without other accompanying symptoms. Viral antibodies screening revealed positivity for all the three specific COVID-19 antibodies. Further haematological evaluation with bone marrow aspiration revealed non-specific dysplastic features of the red cell and megakaryocyte progenitors. Although haematological alterations due to COVID-19 infection are available from adult patients’ reports, the effect of COVID-19 infection in the pediatric population is underestimated and this is the first case with such haematological involvement. Noteworthy, in the current case, the impact of the COVID-19 infection was not related to the severity of the disease, as the symptoms were mild. In similar cases, bone marrow aspiration would not be performed as a part of routine work-up. Thus, it is important when evaluating pediatric patients with COVID-19 infection to search and report those alterations in order to better understand the impact and the spectrum of clinical manifestations of the specific viral infection in children and adolescents.

Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients

Blood ◽  
2011 ◽  
Vol 118 (5) ◽  
pp. 1402-1412 ◽  
Author(s):  
Ahmet H. Elmaagacli ◽  
Nina K. Steckel ◽  
Michael Koldehoff ◽  
Yael Hegerfeldt ◽  
Rudolf Trenschel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Human Cytomegalovirus ◽  
Myeloid Leukemia ◽  
Homogeneous Population ◽  
Relapse Risk ◽  
Pp65 Antigenemia ◽  
Hcmv Replication ◽  
The Impact ◽  
Early Human ◽  
Acute Myeloid

Abstract The impact of early human cytomegalovirus (HCMV) replication on leukemic recurrence was evaluated in 266 consecutive adult (median age, 47 years; range, 18-73 years) acute myeloid leukemia patients, who underwent allogeneic stem cell transplantation (alloSCT) from 10 of 10 high-resolution human leukocyte Ag-identical unrelated (n = 148) or sibling (n = 118) donors. A total of 63% of patients (n = 167) were at risk for HCMV reactivation by patient and donor pretransplantation HCMV serostatus. In 77 patients, first HCMV replication as detected by pp65-antigenemia assay developed at a median of 46 days (range, 25-108 days) after alloSCT. Taking all relevant competing risk factors into account, the cumulative incidence of hematologic relapse at 10 years after alloSCT was 42% (95% confidence interval [CI], 35%-51%) in patients without opposed to 9% (95% CI, 4%-19%) in patients with early pp65-antigenemia (P < .0001). A substantial and independent reduction of the relapse risk associated with early HCMV replication was confirmed by multivariate analysis using time-dependent covariate functions for grades II to IV acute and chronic graft-versus-host disease, and pp65-antigenemia (hazard ratio = 0.2; 95% CI, 0.1-0.4, P < .0001). This is the first report that demonstrates an independent and substantial reduction of the leukemic relapse risk after early replicative HCMV infection in a homogeneous population of adult acute myeloid leukemia patients.

RESPONSE OF STOCK MARKET DURING COVID-19 AND 2008 FINANCIAL CRISIS: A COMPARATIVE EVIDENCE FROM BRICS NATIONS

2021 ◽  
pp. 1-24
Author(s):  
SANJEEV KUMAR ◽  
JASPREET KAUR ◽  
MOSAB I. TABASH ◽  
DANG K. TRAN ◽  
RAJ S DHANKAR
Keyword(s):  
South Africa ◽  
Financial Crisis ◽  
Stock Market ◽  
Stock Returns ◽  
Stock Markets ◽  
2008 Financial Crisis ◽  
First Case ◽  
Egarch Model ◽  
The 2008 Financial Crisis ◽  
The Impact

This study attempts to examine the response of stock markets amid the COVID-19 pandemic on prominent stock markets of the BRICS nation and compare it with the 2008 financial crisis by employing the GARCH and EGARCH model. First, average and variance of stock returns are tested for differences before and after the pandemic, t-test and F-test were applied. Further, OLS regression was applied to study the impact of COVID-19 on the standard deviation of returns using daily data of total cases, total deaths, and returns of the indices from the date on which the first case was reported till June 2020. Second, GARCH and EGARCH models are employed to compare the impact of COVID-19 and the 2008 financial crisis on the stock market volatility by using the data of respective stock indices for the period 2005–2020. The results suggest that the increasing number of COVID-19 cases and reported death cases hurt stock markets of the five countries except for South Africa in the latter case. The findings of the GARCH and EGARCH model indicate that for India and Russia, the financial crisis of 2008 has caused more stock volatility whereas stock markets of China, Brazil, and South Africa have been more volatile during the COVID-19 pandemic. The study has practical implications for investors, portfolio managers, institutional investors, regulatory institutions, and policymakers as it provides an understanding of stock market behavior in response to a major global crisis and helps them in taking decisions considering the risk of these events.

Effect of Buoyancy and Density Ratio on Heat Transfer in a Smooth Cooling Channel of a Gas Turbine Blade

2018 ◽  
Author(s):  
Mandana S. Saravani ◽  
Saman Beyhaghi ◽  
Ryoichi S. Amano
Keyword(s):  
Heat Transfer ◽  
Rotational Speed ◽  
Cfd Simulation ◽  
Density Ratio ◽  
Reynolds Numbers ◽  
Buoyancy Effect ◽  
Square Channel ◽  
First Case ◽  
Computational Fluid Dynamics Cfd ◽  
The Impact

The present work investigates the effects of buoyancy and density ratio on the thermal performance of a rotating two-pass square channel. The U-bend configuration with smooth walls is selected for this study. The channel has a square cross-section with a hydraulic diameter of 5.08 cm (2 inches). The lengths of the first and second passes are 514 mm and 460 mm, respectively. The turbulent flow enters the channel with Reynolds numbers of up to 34,000. The rotational speed varies from 0 to 600 rpm with the rotational numbers up to 0.75. For this study, two approaches are considered for tracking the buoyancy effect on heat transfer. In the first case, the density ratio is set constant, and the rotational speed is varied. In the second case, the density ratio is changed in the stationary case, and the effect of density ratio is discussed. The range of Buoyancy number along the channel is 0–6. The objective is to investigate the impact of Buoyancy forces on a broader range of rotation number (0–0.75) and Buoyancy number scales (0–6), and their combined effects on heat transfer coefficient for a channel with aspect ratio of 1:1. Several computational fluid dynamics (CFD) simulation are carried out for this study, and some of the results are validated against experimental data.

scholarly journals Intrahost Dynamics of Human Cytomegalovirus Variants Acquired by Seronegative Glycoprotein B Vaccinees

2018 ◽  
Vol 93 (5) ◽  
Author(s):  
Cody S. Nelson ◽  
Diana Vera Cruz ◽  
Melody Su ◽  
Guanhua Xie ◽  
Nathan Vandergrift ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Rational Design ◽  
Hcmv Infection ◽  
Vaccine Trial ◽  
The United States ◽  
Glycoprotein B ◽  
Viral Population ◽  
Vaginal Fluid ◽  
The Impact ◽  
Placebo Recipients

ABSTRACTHuman cytomegalovirus (HCMV) is the most common congenital infection worldwide and a frequent cause of hearing loss and debilitating neurologic disease in newborn infants. Thus, a vaccine to prevent HCMV-associated congenital disease is a public health priority. One potential strategy is vaccination of women of child bearing age to prevent maternal HCMV acquisition during pregnancy. The glycoprotein B (gB) plus MF59 adjuvant subunit vaccine is the most efficacious tested clinically to date, demonstrating 50% protection against primary HCMV infection in a phase 2 clinical trial. Yet, the impact of gB/MF59-elicited immune responses on the population of viruses acquired by trial participants has not been assessed. In this analysis, we employed quantitative PCR as well as multiple sequencing methodologies to interrogate the magnitude and genetic composition of HCMV populations infecting gB/MF59 vaccinees and placebo recipients. We identified several differences between the viral dynamics in acutely infected vaccinees and placebo recipients. First, viral load was reduced in the saliva of gB vaccinees, though not in whole blood, vaginal fluid, or urine. Additionally, we observed possible anatomic compartmentalization of gB variants in the majority of vaccinees compared to only a single placebo recipient. Finally, we observed reduced acquisition of genetically related gB1, gB2, and gB4 genotype “supergroup” HCMV variants among vaccine recipients, suggesting that the gB1 genotype vaccine construct may have elicited partial protection against HCMV viruses with antigenically similar gB sequences. These findings suggest that gB immunization had a measurable impact on viral intrahost population dynamics and support future analysis of a larger cohort.IMPORTANCEThough not a household name like Zika virus, human cytomegalovirus (HCMV) causes permanent neurologic disability in one newborn child every hour in the United States, which is more than that for Down syndrome, fetal alcohol syndrome, and neural tube defects combined. There are currently no established effective measures to prevent viral transmission to the infant following HCMV infection of a pregnant mother. However, the glycoprotein B (gB)/MF59 vaccine, which aims to prevent pregnant women from acquiring HCMV, is the most successful HCMV vaccine tested clinically to date. Here, we used viral DNA isolated from patients enrolled in a gB vaccine trial who acquired HCMV and identified several impacts that this vaccine had on the size, distribution, and composition of thein vivoviral population. These results have increased our understanding of why the gB/MF59 vaccine was partially efficacious, and such investigations will inform future rational design of a vaccine to prevent congenital HCMV.

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