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Transplant Infectious Disease : An... Apr 2024Adenovirus infection (ADVi) is an emergent complication in adult patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated...
BACKGROUND
Adenovirus infection (ADVi) is an emergent complication in adult patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with poor outcome. Available data on risk factors and optimal management of ADVi in adult allo-HSCT recipients are limited, and recommendations on monitoring and pre-emptive therapy are mainly based on pediatric data.
METHODS
In this single-center, retrospective study, we reported all cases of positive ADV-DNA from adult patients undergoing allo-HSCT in the period 2014-2019. The study aimed to describe the incidence of ADVi at day +180 post-transplant. Secondly to describe timing, clinical presentation, risk factors, and outcome of ADVi and to analyze the application of a screening strategy in our cohort.
RESULTS
In 445 allo-HSCT recipients, the day +180 incidence was: 9% (39/445) for ADVi, 5% (24/445) for ADV viremia (ADVv), and 3% (15/445) for localized ADVi. The median time to ADVi was 65 (IQR 19; 94) days after HSCT. ADVv-related mortality was 13% (3/24), all cases occurring with blood max-ADV-DNA > 10^3 cp/mL. Independent risk factors for ADVi were diagnosis of lymphoproliferative disease (p = .011) and acute graft-versus-host-disease (p = .021).
CONCLUSIONS
In our cohort, ADVi and ADVv were more frequent than previously reported. ADVv with max-ADV-DNA > 10^3 cp/mL was associated with ADV-related mortality, thus careful monitoring and early initiation of treatment are advisable.
Topics: Adult; Child; Humans; Retrospective Studies; Incidence; Adenoviridae Infections; Adenoviridae; Hematopoietic Stem Cell Transplantation; DNA; Graft vs Host Disease
PubMed: 38192010
DOI: 10.1111/tid.14215 -
PLoS Pathogens Dec 2021Mammalian adenoviruses (AdVs) comprise more than ~350 types including over 100 human (HAdVs) and just three mouse AdVs (MAdVs). While most HAdVs initiate infection by...
Mammalian adenoviruses (AdVs) comprise more than ~350 types including over 100 human (HAdVs) and just three mouse AdVs (MAdVs). While most HAdVs initiate infection by high affinity/avidity binding of their fiber knob (FK) protein to either coxsackievirus AdV receptor (CAR), CD46 or desmoglein (DSG)-2, MAdV-1 (M1) infection requires arginine-glycine-aspartate (RGD) binding integrins. To identify the receptors mediating MAdV infection we generated five novel reporter viruses for MAdV-1/-2/-3 (M1, M2, M3) transducing permissive murine (m) CMT-93 cells, but not B16 mouse melanoma cells expressing mCAR, human (h) CD46 or hDSG-2. Recombinant M1 or M3 FKs cross-blocked M1 and M3 but not M2 infections. Profiling of murine and human cells expressing RGD-binding integrins suggested that αvβ6 and αvβ8 heterodimers are associated with M1 and M3 infections. Ectopic expression of mβ6 in B16 cells strongly enhanced M1 and M3 binding, infection, and progeny production comparable with mαvβ6-positive CMT-93 cells, whereas mβ8 expressing cells were more permissive to M1 than M3. Anti-integrin antibodies potently blocked M1 and M3 binding and infection of CMT-93 cells and hαvβ8-positive M000216 cells. Soluble integrin αvβ6, and synthetic peptides containing the RGDLXXL sequence derived from FK-M1, FK-M3 and foot and mouth disease virus coat protein strongly interfered with M1/M3 infections, in agreement with high affinity interactions of FK-M1/FK-M3 with αvβ6/αvβ8, determined by surface plasmon resonance measurements. Molecular docking simulations of ternary complexes revealed a bent conformation of RGDLXXL-containing FK-M3 peptides on the subunit interface of αvβ6/β8, where the distal leucine residue dips into a hydrophobic pocket of β6/8, the arginine residue ionically engages αv aspartate215, and the aspartate residue coordinates a divalent cation in αvβ6/β8. Together, the RGDLXXL-bearing FKs are part of an essential mechanism for M1/M3 infection engaging murine and human αvβ6/8 integrins. These integrins are highly conserved in other mammals, and may favour cross-species virus transmission.
Topics: Adenoviridae; Adenoviridae Infections; Animals; Antigens, Neoplasm; Humans; Integrins; Mice; Receptors, Virus
PubMed: 34910784
DOI: 10.1371/journal.ppat.1010083 -
The American Journal of Surgical... Sep 2023A recent increase in reports of severe acute hepatitis of unknown etiology in children is under investigation. Although adenovirus has been frequently detected, its role...
A recent increase in reports of severe acute hepatitis of unknown etiology in children is under investigation. Although adenovirus has been frequently detected, its role remains unclear, and systematic histopathologic analysis is lacking. We conducted a retrospective study of 11 children hospitalized between October 2021 and May 2022 with unexplained acute hepatitis and concurrent adenovirus infection. Liver biopsies collected shortly after admission demonstrated moderately to severely active hepatitis in 8/11 (73%) cases, characterized by marked portal mixed inflammation, moderate-to-severe interface activity, and milder lobular inflammation. Clusters of plasma cells were present in 6/11 (55%) cases, mimicking autoimmune hepatitis. Semiquantitative scoring of 17 discrete histologic features found that greater degrees of portal inflammation, interface activity, bile duct injury, bile ductular reaction, lobular inflammation, Kupffer cell activation, and hepatocyte focal necrosis were significantly more common in these cases in comparison to the control group of unexplained acute severe hepatitis without adenovirus infection. Liver biopsy immunohistochemistry was negative for adenovirus in all cases. Polymerase chain reaction testing of liver tissue was positive for the enteric adenovirus serotypes 41 (species F) in 10/11 (91%) cases. An immunoprofile study of hepatic infiltrating lymphocytes in 1 patient revealed the presence of large numbers of CD3 + and CD4 + lymphocytes. Nine patients received supportive treatment without steroids and recovered without the need for liver transplantation. In summary, liver injury in children with severe acute hepatitis and adenovirus infection is characterized by a hepatitic pattern that resembles severe autoimmune hepatitis and may represent an immune-mediated process associated with viral infection.
Topics: Humans; Child; Hepatitis, Autoimmune; Retrospective Studies; Liver; Inflammation; Adenoviridae Infections; CD4-Positive T-Lymphocytes
PubMed: 37357941
DOI: 10.1097/PAS.0000000000002084 -
MMWR. Morbidity and Mortality Weekly... May 2022During October-November 2021, clinicians at a children's hospital in Alabama identified five pediatric patients with severe hepatitis and adenovirus viremia upon...
During October-November 2021, clinicians at a children's hospital in Alabama identified five pediatric patients with severe hepatitis and adenovirus viremia upon admission. In November 2021, hospital clinicians, the Alabama Department of Public Health, the Jefferson County Department of Health, and CDC began an investigation. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.
Topics: Acute Disease; Adenoviridae Infections; Alabama; Child; Hepatitis; Humans; Public Health
PubMed: 35511732
DOI: 10.15585/mmwr.mm7118e1 -
The Journal of Pediatrics Aug 2023To evaluate whether the nature and severity of non-A-E severe acute hepatitis in children noted by the World Health Organization from late 2021 through early 2022 was...
OBJECTIVE
To evaluate whether the nature and severity of non-A-E severe acute hepatitis in children noted by the World Health Organization from late 2021 through early 2022 was indeed increased in 2021-2022 compared with prior years.
STUDY DESIGN
We performed a single-center, retrospective study to track the etiology and outcomes of children with non-A-E severe acute hepatitis in 2021-2022 compared with the prior 3-year periods (2018-2019, 2019-2020, and 2020-2021). We queried electronic medical records of children ≤16 years of age with alanine or aspartate aminotransferase levels of >500 IU. Data were analyzed for the periods of October 1, 2021, to May 1, 2022, and compared with the same time periods in 2018-2021.
RESULTS
Of 107 children meeting entry criteria, 82 cases occurred from October to May of 2018-2022. The average annual case number was 16.3 in 2018-2021 compared with a 2-fold increase (to 33) in 2021-2022 (P = .0054). Analyses of etiologies showed that this increase was associated with a higher number of children who tested positive for viruses (n = 16) when compared with the average of 3.7 for 2018-2021 (P = .018). Adenovirus (26.1%) and severe acute respiratory syndrome coronavirus-2 (10.3%) were the most frequently detected viruses in 2021-2022. Despite evidence of acute liver failure in 37.8% of children in the entire cohort and in 47% of those with viral infection, the overall survival rate was high at 91.4% and 88.9%, respectively.
CONCLUSIONS
The number of children with severe acute hepatitis in our center increased from 2021 to May 2022, with a greater frequency of cases associated with adenovirus, yet transplant-free survival remains high.
Topics: Humans; Child; Adenoviridae; Retrospective Studies; Incidence; COVID-19; Hepatitis; Adenoviridae Infections
PubMed: 37088181
DOI: 10.1016/j.jpeds.2023.113439 -
Poultry Science Nov 2020Outbreaks of inclusion body hepatitis (IBH) and adenoviral gizzard erosion have been anecdotally reported in Greece since approximately 2011. However, a relevant...
Outbreaks of inclusion body hepatitis (IBH) and adenoviral gizzard erosion have been anecdotally reported in Greece since approximately 2011. However, a relevant increase in clinical outbreaks compatible with IBH has been described since 2014. Unfortunately, with limited exceptions, only serological assays were performed, and involved strains were not properly characterized. In the present study, 35 outbreaks were investigated in the period between July 2017 and February 2018 in Greece. In addition to clinical and histopathological diagnosis, fowl adenovirus (FAdV) presence was investigated by PCR and sequencing. Thirty-four out of 35 samples tested FAdV positive. Twenty-nine (85.29%) and 5 (14.71%) strains were classified as FAdV-E and FAdV-D, respectively. Fowl adenovirus-E strains were genetically homogeneous and formed an independent cluster of Greek-only sequences, including the sole previously available sequence, suggesting the prolonged circulation of this species in Greece. On the contrary, FAdV-D strains were more heterogeneous and closely related to strains sampled in other European countries, testifying the occurrence of multiple introduction events. The evaluation of phylogenetic relationships, geographic clustering, age of infection, and origin of the broiler breeder flocks suggests that both vertical and horizontal transmission are important in FAdV epidemiology in Greece and highlights the limited efficacy of currently implemented control measures. Of note, a significantly higher mortality was observed in precociously infected flocks, likely because of the higher susceptibility of younger animals. This evidence stresses the need of preventing vertical and/or early infection to limit the economic impact of adenovirus-induced diseases.
Topics: Adenoviridae Infections; Animals; Aviadenovirus; Chickens; Europe; Greece; Molecular Epidemiology; Phylogeny; Poultry Diseases
PubMed: 33142516
DOI: 10.1016/j.psj.2020.07.019 -
Infectious Disorders Drug Targets 2023Adenovirus generally causes upper and lower respiratory tract infections. It is common in children and occasionally in adults. Neurological involvement is rare, which...
BACKGROUND
Adenovirus generally causes upper and lower respiratory tract infections. It is common in children and occasionally in adults. Neurological involvement is rare, which may be mild aseptic meningitis to potentially fatal acute necrotizing encephalopathy. Recently, viruses have been reported increasingly to cause CNS infections. Viral aetiology typically varies with age.
CASE PRESENTATION
Here, we report an unusual adenovirus meningoencephalitis with a co-infection of neurocysticercosis in an immunocompetent adult patient. An 18-year-old healthy female student was admitted with fever and headache for 11 days and progressive altered behaviour for 5 days, followed by altered sensorium for 3 days. This variable and unusual presentation of adenoviral infection involving CNS provoked diagnostic difficulties, but with the help of advanced diagnostics, especially molecular, exact aetiology was detected. Even with the neurocysticercosis infection in this patient, the outcome was not adversely affected.
CONCLUSION
This unusual co-infection with a successful outcome is the first case of this type in literature.
Topics: Child; Adult; Humans; Female; Adolescent; Neurocysticercosis; Coinfection; Adenoviridae Infections; Adenoviridae; Meningoencephalitis
PubMed: 36999426
DOI: 10.2174/1871526523666230329123428 -
Viruses Jun 2024Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine, and... (Review)
Review
Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine, and oncology applications, Ad-based platforms offer advantages, including ease of genetic manipulation, scale of production, and well-established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that must be overcome for adenovirus-based therapies to be truly efficacious. Both pre-existing anti-Ad immunity in the population as well as the rapid development of an immune response against engineered adenoviral vectors can have detrimental effects on the downstream impact of an adenovirus-based therapeutic. This review focuses on the different challenges posed, including pre-existing natural immunity and anti-vector immunity induced by a therapeutic, in the context of innate and adaptive immune responses. We summarise different approaches developed with the aim of tackling these problems, as well as their outcomes and potential future applications.
Topics: Humans; Adenoviridae; Genetic Vectors; Genetic Therapy; Adaptive Immunity; Animals; Immunity, Innate; Immune System; Adenoviridae Infections
PubMed: 38932265
DOI: 10.3390/v16060973 -
Viruses Aug 2023Astroviruses (AstV) and adenoviruses (AdV) are associated with diarrhoea in young animals. However, the epidemiology and genetic diversity of AstVs and AdVs in animals...
Astroviruses (AstV) and adenoviruses (AdV) are associated with diarrhoea in young animals. However, the epidemiology and genetic diversity of AstVs and AdVs in animals is not well studied. Hence, the present study was conducted to detect and characterize AstVs and AdVs in calves, piglets and puppies from Western Maharashtra, India. Out of the processed porcine (48), canine (80), and bovine (65) faecal samples, the porcine AstV (PAstV), bovine AstV (BAstV), canine AstV (CAstV), and porcine AdV (PAdV) were detected in 12.5%, 7.69%, 3.75% and 4.1% of samples, respectively. In the RNA-dependent RNA polymerase region-based phylogenetic analysis, the detected BAstV strains grouped with MAstV-28, MAstV-33, and MAstV-35, CAstV strains belonged to MAstV-5; PAstV strains belonged to MAstV-24, MAstV-26, and MAstV-31. However, in hexon gene-based phylogeny, both the detected PAdV were of genotype 3, exhibiting 91.9-92.5% nucleotide identity with Ivoirian and Chinese strains. The study reports first-time BAstVs from calves and PAdV-3 from piglets in India. The study revealed diversity in the circulation of AstVs in tested animals and AdVs in pigs, and suggested that they alone might be associated with other diarrhoea or in combination with other enteric pathogens, thus highlighting the necessity of extensive epidemiological investigations to develop diagnostic tools and control measures.
Topics: Animals; Cattle; Dogs; Swine; Adenoviridae; Phylogeny; India; Adenoviridae Infections; Astroviridae; Canidae; Diarrhea
PubMed: 37632021
DOI: 10.3390/v15081679 -
Viruses Jul 2023Worldwide, acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children under 5 years of age. Viruses, including norovirus, rotavirus, and enteric...
Worldwide, acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children under 5 years of age. Viruses, including norovirus, rotavirus, and enteric adenovirus, are the leading causes of pediatric AGE. In this prospective cohort study, we investigated the viral load and duration of shedding of norovirus, rotavirus, and adenovirus in stool samples collected from 173 children (median age: 15 months) with AGE who presented to emergency departments (EDs) across Canada on Day 0 (day of enrollment), and 5 and 28 days after enrollment. Quantitative RT-qPCR was performed to assess the viral load. On Day 0, norovirus viral load was significantly lower compared to that of rotavirus and adenovirus ( < 0.001). However, on Days 5 and 28, the viral load of norovirus was higher than that of adenovirus and rotavirus ( < 0.05). On Day 28, norovirus was detected in 70% (35/50) of children who submitted stool specimens, while rotavirus and adenovirus were detected in 52.4% (11/24) and 13.6% (3/22) of children ( < 0.001), respectively. Overall, in stool samples of children with AGE who presented to EDs, rotavirus and adenovirus had higher viral loads at presentation compared to norovirus; however, norovirus was shed in stool for the longest duration.
Topics: Child; Humans; Infant; Child, Preschool; Rotavirus; Adenoviridae; Norovirus; Prospective Studies; Gastroenteritis; Adenoviridae Infections; Feces; Rotavirus Infections; Caliciviridae Infections
PubMed: 37515227
DOI: 10.3390/v15071541